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Sample records for schirrous invasive ductal

  1. Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast.

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    Arps, David P; Healy, Patrick; Zhao, Lili; Kleer, Celina G; Pang, Judy C

    2013-04-01

    Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.

  2. Invasive ductal carcinoma vs. invasive lobular carcinoma; mammographic findings

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    Lee, Eun Chun; Do, Young Soo; Oh, Hoon Il; Han, Yoon Hee; Kim, Ki Soo; Chin, Soo Yil [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-01-01

    The purpose of this study is to evaluate mammographic findings of invasive ductal carcinoma (IDC) and invasive lobular carcinoma(ILC) and to find differential points between the two. 239 patients, who underwent mammography prior to surgery and were proved to have IDC(patients) or ILC(15 patients) pathologically, were analized retrospectively. On mammogram, presence of mass and microcalcification were analized. When there was a mass on mammogram, lesion opacity was classified into high, equal, or low opacity and border of the mass was classified into spiculated, poorly marginated, and well-marginated. When there was no definite mass, mammographic findings were classifie into asymmetric opacity and no mass. Masses were observed in 168 patients(75%) of IDC and 12 patients(80%) of ILC. Border of the masses were spiculated(n=50, 22.3%), poorly marginated(n=112, 50%), or well-marginated(n=6, 2.7%) in patients with IDC. Spiculated and poorly marginated borders were observed in 8 patients(53.3%) and 4 patients(26.7%) respectively, in patients with ILC. Microcalcifications were seen in 88 patients(17.3%) of IDC and patients(33.3%) of ILC. Although equal or low opacities were observed more frequently in ILC and microcalcifications were noted more frequently in IDC, it was difficult to differentiate the two diseases based on mammographic findings.

  3. Invasive ductal carcinoma vs. invasive lobular carcinoma; mammographic findings

    International Nuclear Information System (INIS)

    Lee, Eun Chun; Do, Young Soo; Oh, Hoon Il; Han, Yoon Hee; Kim, Ki Soo; Chin, Soo Yil

    1996-01-01

    The purpose of this study is to evaluate mammographic findings of invasive ductal carcinoma (IDC) and invasive lobular carcinoma(ILC) and to find differential points between the two. 239 patients, who underwent mammography prior to surgery and were proved to have IDC(patients) or ILC(15 patients) pathologically, were analized retrospectively. On mammogram, presence of mass and microcalcification were analized. When there was a mass on mammogram, lesion opacity was classified into high, equal, or low opacity and border of the mass was classified into spiculated, poorly marginated, and well-marginated. When there was no definite mass, mammographic findings were classifie into asymmetric opacity and no mass. Masses were observed in 168 patients(75%) of IDC and 12 patients(80%) of ILC. Border of the masses were spiculated(n=50, 22.3%), poorly marginated(n=112, 50%), or well-marginated(n=6, 2.7%) in patients with IDC. Spiculated and poorly marginated borders were observed in 8 patients(53.3%) and 4 patients(26.7%) respectively, in patients with ILC. Microcalcifications were seen in 88 patients(17.3%) of IDC and patients(33.3%) of ILC. Although equal or low opacities were observed more frequently in ILC and microcalcifications were noted more frequently in IDC, it was difficult to differentiate the two diseases based on mammographic findings

  4. Invasive ductal carcinoma within fibroadenoma and lung metastases

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    Abu-Rahmeh, Zuhair; Nseir, William; Naroditzky, Inna

    2012-01-01

    Fibroadenomas are one of the most common benign tumors of the breast. Malignant transformation from fibroadenoma to cancer is rare. We present a case of an invasive ductal carcinoma within an otherwise benign fibroadenoma with lung metastasis in a 69-year-old woman. PMID:22259257

  5. Invasive ductal carcinoma within fibroadenoma: a case report

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    2009-01-01

    Introduction Fibroadenoma is the most common benign tumor of the female breast with the highest incidence before age 30. Fibroadenoma may be associated with fibrocystic changes, proliferative epithelial changes, and extremely rarely, with non-invasive and invasive cancer. Case presentation We present a rare case of a 39 years old female with invasive ductal carcinoma arising within fibroadenoma. Conclusion There is a low percentage of fibroadenomas harboring carcinoma; however, all breast lumps should be seriously managed; extirpation and histological examination is recommended. PMID:19946485

  6. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

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    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-04-04

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

  7. Invasive ductal breast cancer metastatic to the sigmoid colon

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    Zhou Xiao-cong

    2012-11-01

    Full Text Available Abstract The most common sites of breast cancer metastasis are the bone, lung, liver and brain. However, colonic metastases from breast cancer are very rare in the clinic. We describe an unusual case of sigmoid colonic metastasis from invasive ductal breast cancer. With this report, we should increase the clinical awareness that any patient with a colorectal lesion and a history of malignancy should be considered to have a metastasis until proven otherwise. Early diagnosis is very important, which enables prompt initiation of systemic treatment, such as chemotherapy, endocrine therapy or both, thus avoiding unnecessary radical surgical resection and improving the prognosis.

  8. Large mammary hamartoma with focal invasive ductal carcinoma

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    Pervatikar Suneet

    2009-04-01

    Full Text Available Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.

  9. Mucinous subtype of invasive ductal carcinoma arising within a fibroadenoma.

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    Monsefi, Nahid; Nikpour, Hossein; Safavi, Moienadin; Lashkarizadeh, Mohammad Reza; Dabiri, Shahriar

    2013-06-01

    Fibroadenoma is a common benign tumor observed during the second and third decades of life. Malignancy transformation in the epithelial component of a fibroadenoma is rare and can occur 20 years after its diagnosis. Mammographic findings in this phenomenon include indistinct margins and microcalcifications. Here we present a 58-year-old woman with a mobile, lateral upper quadrant mass that was rather firm when palpated. The mammography showed a lobulated mass without calcification suggestive of a benign process, most probably fibroadenoma. However the excisional biopsy contained both an intracanalicular fibroadenoma and invasive ductal carcinoma with mucinous components.

  10. CLINICAL RELEVANCE OF COEXISTENCE OF DUCTAL CA IN SITU AND INVASIVE DUCTAL CARCINOMA OF BREAST

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    Kirithiga Ramalingam

    2017-06-01

    Full Text Available BACKGROUND There are many studies reported in the literature with respect to the Ductal Carcinoma in Situ (DCIS progressing into Invasive Ductal Carcinoma (IDC of the breast. However, there is hardly any study on the coexistence of both and its clinical significance. The aim of the study is to analyse the clinical and pathological parameters of synchronous DCIS and IDC to predict the prognostic factors. MATERIALS AND METHODS 42 patients with a final pathological diagnosis of synchronous DCIS and IDC diagnosed in 2009-11 were included in the study. Statistical analysis was done using SPSS software utilising the appropriate analytical methods. RESULTS Majority of the patients in this study group presented with early breast cancer (64.3%. Forty eight percent were Her2 subtype (ER, PR negative and HER2/neu-positive and 31% were triple negative. Eighty one percent of the IDC associated histology was Not Otherwise Specified (NOS type. Grade 3 lesions were more common (57%. Recurrence of the disease occurred in 66% of patients during a mean duration of follow up of 3.6 years with predominance of visceral metastasis (51.5%. Recurrence was more common in node positive disease (59.5%, those with lymphovascular emboli (59.5% and perinodal spread (76% on histopathological examination. CONCLUSION Synchronous DCIS and IDC disease entity appears to have an aggressive nature compared to the course of IDC alone entity. Prognostic factors relating to IDC appears to correlate well with recurrence than that of the prognostic factors of DCIS component in such synchronous setting.

  11. [Triexponential diffusion analysis in invasive ductal carcinoma and fibroadenoma].

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    Nakagawa, Masayuki; Miyati, Tosiaki; Hayashi, Tatsuya; Kanao, Syotaro; Taniguchi, Masahiro; Higashimura, Kyoji; Toi, Masakazu; Togashi, Kaori

    2014-03-01

    To simultaneously obtain information on diffusion and perfusion in breast lesions by diffusion-weighted magnetic resonance imaging (DWI), we analyzed three diffusion components using a triexponential function. Eighteen subjects [10 with invasive ductal carcinoma (IDC), 8 with fibroadenoma] were evaluated using DWI with multiple b-values. We derived perfusion-related diffusion, fast free diffusion, and slow restricted diffusion coefficients (Dp, Df, Ds) calculated from the triexponential function using the DWI data. Moreover, the triexponential analysis was compared with biexponential and monoexponential analyses. Each diffusion coefficient with a triexponential function was correlated to a relative enhancement ratio (RER) using dynamic contrast-enhanced MRI. In triexponential analysis, Dp and Ds in IDC were significantly higher than those for fibroadenoma. There was no correlation between each diffusion coefficient from the triexponential analysis in any of the groups (Dp, Df, and Ds), but biexponential analysis revealed a positive correlation between each diffusion coefficient in breast lesions. Strong correlations were found between Dp and RERs. Triexponential analysis thus makes it possible to obtain, in noninvasive fashion, more detailed diffusion and perfusion information in breast lesions.

  12. Invasive ductal carcinoma of the breast in a 14-year-old girl

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    Kim, Joo Yeon; Kim, Yun Ju; Kim, Sung Hun; Kang, Bong Joo [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Department of Radiology, Seoul (Korea, Republic of); Song, Byung Joo [The Catholic University of Korea, Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  13. Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.

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    Ballard, Ashley James

    2015-12-01

    The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types. Copyright © 2015 Elsevier GmbH. All rights reserved.

  14. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer

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    Truin, W.; Voogd, A.C.; Vreugdenhil, G.; van der Heiden-van der Loo, M.; Siesling, Sabine; Roumen, R.M.

    2012-01-01

    Background On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Patients and methods Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast

  15. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma.

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    Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

    2016-03-25

    The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9% and 88.4% for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6% and 93.1% for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC.

  16. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.

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    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-01-23

    We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC ( p cancers, HSL and FABP4 were more highly expressed in ILC ( p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity ( p = 0.004) and acyl-CoA oxidase 1 positivity ( p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity ( p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  17. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

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    Yoon Jin Cha

    2017-01-01

    Full Text Available We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC and invasive ductal carcinoma (IDC of the breast. A total of 584 breast cancers (108 ILC and 476 IDC were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL, perilipin A, fatty acid binding protein (FABP4, carnitine palmitoyltransferase (CPT-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN. HSL, perilipin A, and FABP4 expression (all p < 0.001 differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001 and perilipin A in luminal A-type IDC (p = 0.007. Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001. Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004 and acyl-CoA oxidase 1 positivity (p = 0.032 and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027. In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  18. Is axillary sonographic staging less accurate in invasive lobular breast cancer than in ductal breast cancer?

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    Sankaye, Prashant; Chhatani, Sharmila; Porter, Gareth; Steel, Jim; Doyle, Sarah

    2014-10-01

    The purpose of this study was to determine whether axillary sonography is less accurate in invasive lobular breast cancer than in ductal breast cancer. Patients with invasive breast cancer were retrospectively identified from histologic records from 2010 to 2012. Staging axillary sonograms from 96 patients with primary breast cancer in each of 2 subgroups, invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), were reviewed. Preoperative sonographically guided 14-gauge core biopsy was performed on morphologically abnormal lymph nodes. Thirty-one of 96 patients (32%) in each subgroup were node positive on final postoperative histopathologic analysis. Axillary staging sensitivity was 17 of 31 patients (54%) in the IDC subgroup and 15 of 31(48%) in the ILC subgroup. Further analysis of the data showed no statistically significant differences between these subgroups. We found that there was no statistically significant difference in the accuracy of axillary sonographic staging between ILC and IDC. © 2014 by the American Institute of Ultrasound in Medicine.

  19. Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.

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    Arps, David P; Jorns, Julie M; Zhao, Lili; Bensenhaver, Jessica; Kleer, Celina G; Pang, Judy C

    2014-12-01

    Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies. Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed. For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L. Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.

  20. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

    2016-01-01

    The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9 % and 88.4 % for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6 % and 93.1 % for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC. The online version of this article (doi:10.1186/s12885

  1. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

    Science.gov (United States)

    Truin, W; Voogd, A C; Vreugdenhil, G; van der Heiden-van der Loo, M; Siesling, S; Roumen, R M

    2012-11-01

    On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

  2. Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

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    Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

    2017-08-15

    Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

  3. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI......) with those obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ...

  4. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI...... obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ lesions...

  5. Invasive Ductal Carcinoma of Breast : Correlation between Sonographic Posterior Acoustic Patterns with Histopathology

    International Nuclear Information System (INIS)

    Cho, Hyun Cheol; Lee, Yong Woo; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Kim, Dong Sug; Bae, Young Kyung

    1996-01-01

    To evaluate the frequency of posterior sonic attenuation and enhancement in invasive ductal carcinoma of breast on ultrasound, and to compare with histo-pathologic findings. Sonographic findings of 26 histologically proven invasive ductal carcinomas were retrospectively reviewed in point of posterior echo pattern regardless other ultrasonic features. They were classified in two groups according to posterior echo pattern such as enhancement or shadowing, and compared with various internal histologic characteristics such as amount of connective tissue, degree of elastosis, necrosis, gross circumscription,harboring inflammation, histologic differentiation, nuclear pleomorphism, and mitotic index. The acoustic shadowing was seen in 34.6%, whereas posterior sonic enhancement was seen in 65.4% of cases. The acoustic shadowing group had more connective tissue, elastosis, and poor demarcated margin than the sonic enhancement group(p < 0.05). But no significant differences were seen in other histopathologic findings representing malignancy between two groups. A close relationship between posterior echo pattern and amount of connective tissue or elastosis is found in invasive ductal carcinoma of breast. The acoustic shadowing known as a characteristic ultrasonographic finding of malignant breast mass does not represent the degree of malignancy

  6. [Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women].

    Science.gov (United States)

    Karpinska-Kaczmarczyk, Katarzyna

    2009-01-01

    The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node-negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas.

  7. ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Bàrbara Castellana, Daniel Escuin, Gloria Peiró, Bárbara Garcia-Valdecasas, Tania Vázquez, Cristina Pons, Maitane Pérez-Olabarria, Agustí Barnadas, Enrique Lerma

    2012-01-01

    Full Text Available The mechanism of progression from ductal carcinoma in situ (DCIS to invasive ductal carcinoma (IDC remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR and immunohistochemistry. Controls included seven pure in situ carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT.Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, and COL11A1, cellular adhesion (GJB2, cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, and ENPP2, extracellular matrix degradation (MMP11, MMP13, and MMP14, and growth/proliferation (ST6GAL2. qRT-PCR confirmed the expression patterns of ASPN, GJB2, ENPP2, ST6GAL2, and TMBS10. Expression of the ASPN and GJB2 gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors (P < 0.05.Conclusions: The upregulation of ASPN and GJB2 may play important roles in local invasion of breast ductal carcinomas.

  8. Unusual uterine metastasis of invasive ductal carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Tayfur Çift

    2016-09-01

    Full Text Available Metastatic carcinoma of the uterus usually originates from other genital sites. Extragenital metastases such as breast are rare. A woman aged 34 years with a history of breast cancer was referred to the gynecology outpatient clinic for routine follow-up. Diagnostic tests and gynecologic examination revealed a uterine mass, which was removed with laparotomy. The pathologic investigation revealed metastasis of invasive lobular breast cancer. Chemotherapy was given and the patient has been under follow-up for 3 years with normal imaging on comput-erized tomographic examination and positron-emission tomography-computerized tomographic. It should be kept in mind that patients with breast cancer who have received tamoxifen may develop primary endometrial cancers, and may also demonstrate uterine metastases. With successful treatment these patients can obtain dis-ease-free survival.

  9. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

    Directory of Open Access Journals (Sweden)

    Kanika Gupta

    2018-01-01

    Full Text Available Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR Breast Imaging Reporting and Data System (BI-RADS Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001. The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  10. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

    Science.gov (United States)

    Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

    2018-01-01

    Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  11. Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas.

    Science.gov (United States)

    Karpińska-Kaczmarczyk, Katarzyna; Kram, Andrzej; Kaczmarczyk, Mariusz; Domagała, Wenancjusz

    2009-01-01

    The aim of this study was to evaluate associations between seven morphometric parameters of the nucleoli and nuclei of methyl green and pyronin Y (MG-PY) stained tumour cells of invasive ductal breast carcinoma with relapse-free survival (RFS) and overall survival (OS) time. Histological sections from 150 invasive ductal breast cancers were stained with MG-PY and the following parameters were evaluated by computer image analysis: the nucleolar area, long to short nucleolar axis ratio, nucleolar shape parameter assessing the degree of nucleolar roundness, long to short nuclear axis ratio, number of nucleoli in the nucleus and the percentage of the nuclear cross-section surface area occupied by the nucleoli. A statistically significant association between a nucleolar shape polymorphism and the number of nucleoli in the nuclei of tumour cells and the RFS but not OS was found in the entire group of patients as well as patients with axillary lymph node metastases. A higher polymorphism of nucleolar shape and a higher number of nucleoli in the nuclei of breast cancer cells were associated with decreased relapse-free survival (p nucleoli in MG-PY stained histological sections can be useful in the analysis of associations between nucleolar parameters and prognosis of patients with invasive breast cancer.

  12. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

    2015-12-15

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  13. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

    2015-01-01

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  14. Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells

    DEFF Research Database (Denmark)

    Kong, Su Chii; Nøhr-Nielsen, Asbjørn; Zeeberg, Katrine

    2016-01-01

    , localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. RESULTS: MCT1......, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858...

  15. Expression of CPEB4 in invasive ductal breast carcinoma and its prognostic significance

    Directory of Open Access Journals (Sweden)

    Sun HT

    2015-11-01

    Full Text Available Hao-Ting Sun,1,2,* Xin Wen,3,* Tian Han,4,* Zhen-Hua Liu,5 Shao-Bo Li,1 Ji-Gang Wang,1 Xiu-Ping Liu61Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 2Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Canton, Guangdong Province, 4Key Lab of Myopia, Ministry of Health, Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 5Urology Department and Institute of Urology, Peking University First Hospital, Peking University, Beijing, 6Department of Pathology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workAims: Cytoplasmic polyadenylation element binding proteins (CPEBs are RNA-binding proteins that regulate translation by inducing cytoplasmic polyadenylation. CPEB4 has been reported in association with tumor growth, vascularization, and invasion in several cancers. To date, the expression of CPEB4 with clinical prognosis of breast cancer was never reported before. We aim to investigate the expression of CPEB4 and its prognostic significance in invasive ductal breast carcinoma.Methods: Immunohistochemical staining of CPEB4 and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor was performed in 107 invasive ductal carcinoma (IDC samples, and prognostic significance was evaluated.Results: High expression of CPEB4 was observed in 48.6% of IDC samples. Elevated CPEB4 expression was possibly related to increased histological grading (P=0.037 and N stage (P<0.001. Patients with high expression of CPEB4 showed shorter overall survival (P=0.001. High CPEB4 expression was an independent prognostic factor for overall survival (P=0.022, hazard ratio =4.344, 95% confidence interval =1.235–15

  16. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

    Science.gov (United States)

    Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

    2018-04-01

    The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  17. Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study

    NARCIS (Netherlands)

    van Hilst, Jony; de Rooij, Thijs; Klompmaker, Sjors; Rawashdeh, Majd; Aleotti, Francesca; Al-Sarireh, Bilal; Alseidi, Adnan; Ateeb, Zeeshan; Balzano, Gianpaolo; Berrevoet, Frederik; Björnsson, Bergthor; Boggi, Ugo; Busch, Olivier R.; Butturini, Giovanni; Casadei, Riccardo; del Chiaro, Marco; Chikhladze, Sophia; Cipriani, Federica; van Dam, Ronald; Damoli, Isacco; van Dieren, Susan; Dokmak, Safi; Edwin, Bjørn; van Eijck, Casper; Fabre, Jean-Marie; Falconi, Massimo; Farges, Olivier; Fernández-Cruz, Laureano; Forgione, Antonello; Frigerio, Isabella; Fuks, David; Gavazzi, Francesca; Gayet, Brice; Giardino, Alessandro; Bas Groot, Koerkamp; Hackert, Thilo; Hassenpflug, Matthias; Kabir, Irfan; Keck, Tobias; Khatkov, Igor; Kusar, Masa; Lombardo, Carlo; Marchegiani, Giovanni; Marshall, Ryne; Menon, Krish V.; Montorsi, Marco; Orville, Marion; de Pastena, Matteo; Pietrabissa, Andrea; Poves, Ignaci; Primrose, John; Pugliese, Raffaele; Ricci, Claudio; Roberts, Keith; Røsok, Bård; Sahakyan, Mushegh A.; Sánchez-Cabús, Santiago; Sandström, Per; Scovel, Lauren; Solaini, Leonardo; Soonawalla, Zahir; Souche, F. Régis; Sutcliffe, Robert P.; Tiberio, Guido A.; Tomazic, Aleš; Troisi, Roberto; Wellner, Ulrich; White, Steven; Wittel, Uwe A.; Zerbi, Alessandro; Bassi, Claudio; Besselink, Marc G.; Abu Hilal, Mohammed

    2017-01-01

    The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent

  18. PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

    Science.gov (United States)

    Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

    2017-03-28

    Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. ER/PR- tumours demonstrated higher Kep mean and SUV max than ER or PR+ tumours. HER2- tumours displayed higher ADC mean , Kep mean , and SUV max than HER2+tumours. Only ADC mean discriminated Ki67⩽14% tumours (lower ADC mean ) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

  19. Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

    Science.gov (United States)

    Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

    2016-09-01

    Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

  20. Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

    Science.gov (United States)

    Shi, Bibo; Grimm, Lars J; Mazurowski, Maciej A; Baker, Jay A; Marks, Jeffrey R; King, Lorraine M; Maley, Carlo C; Hwang, E Shelley; Lo, Joseph Y

    2018-03-01

    The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  1. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-01-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

  2. Invasive lobular carcinoma of the breast: A special histological type compared with invasive ductal carcinoma

    Science.gov (United States)

    Chen, Zheling; Yang, Jiao; Li, Shuting; Lv, Meng; Shen, Yanwei; Wang, Biyuan; Li, Pan; Yi, Min; Zhao, Xiao’ai; Zhang, Lingxiao; Wang, Le

    2017-01-01

    The clinical outcomes and therapeutic strategies for infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not uniform. The primary objectives of this study were to identify the differences in the clinical characteristics and prognoses between ILC and IDC, and identify the high-risk population based on the hormone receptor status and metastasis sites. The Surveillance, Epidemiology, and End Results Program database was searched and patients diagnosed with ILC or IDC from 1990 to 2013 were identified. In total,796,335 patients were analyzed, including 85,048 withILC (10.7%) and 711,287 withIDC (89.3%). The ILC group was correlatedwith older age, larger tumor size, later stage, lower grade, metastasis disease(M1) disease, and greater counts ofpositive lymph nodesandestrogen-receptor-positive (ER)/progesterone receptor-positive (PR) positive nodes. The overall survival showed an early advantage for ILC but a worse outcome after 5 years. Regarding the disease-specific survival, the IDC cohort had advantages over the ILC group, both during the early years and long-term. In hormone status and metastasis site subgroup analyses, the ER+/PR+ subgroup had the best survival, while the ER+/PR- subgroup had the worst outcome, especially the ILC cohort. ILC and IDC had different metastasis patterns. The proportion of bone metastasis was higher in the ILC group (91.52%) than that in the IDC (76.04%), and the ILC group was more likely to have multiple metastasis sites. Survival analyses showed patients with ILC had a higher risk of liver metastasis (disease-specific survival[DSS]; P = 0.046), but had a better overall survival than the bone metastasis group (P<0.0001). We concluded that the long-term prognosis for ILC was poorer than that for IDC, and the ER+/PR- subgroup had the worst outcome. Therefore, the metastasis pattern and prognosis must be seriously evaluated, and a combination of endocrine therapy and chemotherapy should be considered. PMID

  3. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer.

    Science.gov (United States)

    Truin, Wilfred; Roumen, Rudi M; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J; Tjan-Heijnen, Vivianne C; Voogd, Adri C

    2016-08-01

    Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification outcomes. We evaluated the effect of axillary staging procedures and subsequent axillary nodal status in patients with invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) from 1998 to 2013. The use of SLN biopsy and the nodal status distribution were analyzed in patients with stage T1-T2 ILC and IDC. Logistic regression analysis was performed to determine the independent effect of histologic type on the probability of the presence of isolated tumor cells (ITCs), micrometastases, and macrometastases. A total of 89,971 women were diagnosed, 10,146 with ILC (11%) and 79,825 with IDC (89%). The patients who had undergone SLN biopsy were more frequently diagnosed with ITCs than were those who had undergone axillary lymph node dissection only (odds ratio, 8.8; 95% confidence interval, 7.0-11.2). In 2013, the proportion of patients with ITCs in the axillary nodes was 8% in those with ILC and 4.4% in those with IDC. Patients with ILC were significantly more likely to have ITCs in their axillary lymph nodes than were patients with IDC (odds ratio, 1.8; 95% confidence interval, 1.6-2.0). With the introduction of SLN biopsy and the renewed 2002 TNM classification, patients with ILC have been more frequently diagnosed with ITCs than have patients with IDC. The clinical consequence of this finding must be established from further research. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

  5. 63 Patients and cytokeratin 8/18 expression in breast, atypical ductal hyperplasia, ductal carcinoma in situ and invasive Duct Carcinoma

    International Nuclear Information System (INIS)

    Shamloula, M.M.; El-Shorbagy, S.H.; Saied, E.M.E.

    2007-01-01

    Background and Purpose: The pattern and distribution of 63 Patients expression as a myoepithelia/basal stem cell marker can be different between atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and may denote basal phenotype of breast ductal carcinoma. CK8/18 is a luminal marker and may indicate a luminal phenotype of IDC and its expression in ADH and DCIS may refer to a possible precursor lesion to IDC. This work was designed to study and compare the expression of 63 Patients and cytokeratin 8/18 (CK8/l8) in some cases of ADH, DC IS and IDC. Materials and Methods: Histopathological evaluation and immunohistochemical study of anti- 63 Patients and anti-CK8/l8 was performed on selected archival cases of 7 ADH, 12 DCIS, 30 IDC of known clinico pathological data and previous estrogen receptor status (ER) for IDe. Confirmatory anti-smooth muscle actin (ASMA) expression for positive 63 Patients cases was performed. Results: 63 Patients was expressed in the peripheral rim of the myoepithelial cell layer in ADH and DCIS with occasional gabs in DCrS. It was positive and stained occasional malignant cells in 3/30 (10%) of IDC cases. Confirmatory ASMA staining decorated the same peripheral rim of cells in ADH and DCIS, but was negative in 63 Patients positive IDC cases. CK8/l8 was positive in 100% of ADH, 8/12 (66.7%) of DC IS and 22/30 (73%) of IDC cases. Combined 63 Patients and CK8/ 18 expression was noticed in 3/30 (10%) of IDe. Conclusion: It is concluded from this study that 63 Patients is specific and valuable in differentiating myoepithelial cells and is more specific and valuable than other myoepithelial markers, as ASMA and can differentiate between ADH, DCIS, IDC as it stains peripheral myoepithelial cells in ADH and DCIS with gabs in the latter and does not stain any neoplastic cells. In IDC, it is positive in malignant cells in a minority of cases which may indicate basal/stem cell/myoepithelial cell origin

  6. The influence of aging on pathologic and immunobiologic parameters of invasive ductal breast carcinoma

    Directory of Open Access Journals (Sweden)

    Ivković-Kapicl Tatjana

    2006-01-01

    Full Text Available Background/Aim. Most human cancers, including breast one, increase in frequency with aging. The aim of this study was to explore the hypothesis that aging also alters breast cancer biology. Methods. The study included 120 women with primary invasive ductal carcinoma of the breast. We correlated the patients age and diagnosis with the commonly used clinical, pathological factors and newer tumor biomarkers. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, estrogen (ER, progesterone (PR receptors, and angiogenesis. Results. In our study, the patients with axillary lymph node metastases and negative steroid hormone receptors (ER and PR were significantly younger than the patients with nodal involvement and positive hormone receptors. There was also a significant association between the patients age, diagnosis and angiogenesis. No association was found between the patients age and tumor size, histological grade, p53, c-erbB-2, and Ki-67. Conclusion. The results of our study supported only partially the hypothesis that the breast cancer biology is significantly affected by a patient's age.

  7. Diagnostic and prognostic relevance of Cullin1 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Sohn, Jin Hee; Chae, Seoung Wan; Pyo, Jung-Soo; Park, Chan Heun; Oh, Young-Ha; Jang, Ki-Seok; Kim, Hack-Lyoung; Kim, Min

    2012-10-01

    Cullin1 (Cul1) is a matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins. This enzyme has recently been reported to play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours. 159 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were studied. Cul1 expression was analysed by immunohistochemical staining on a tissue microarray. The relationship between Cul1 expression and clinicopathological parameters was evaluated. Tumour expression of Cul1 was correlated with prognostic factors such as high histological grade and p53 expression, and was also linked to negative ER and positive HER2 as therapeutic markers (all pCul1 expression in both univariate and multivariate analyses (all pCul1 expression was significantly associated with high-grade tumours and poor prognosis, suggesting that it may play a role in breast tumour progression. Cul1 expression may therefore be crucial for the prediction of disease outcome in breast cancer patients.

  8. Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: Ductal carcinoma in situ vs. invasive ductal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nadrljanski, Mirjan, E-mail: dr.m.nadrljanski@gmail.com [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Plešinac-Karapandžić, Vesna; Nikitović, Marina [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Marković-Vasiljković, Biljana [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Milošević, Zorica [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia)

    2014-08-15

    Objectives: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. Materials and Methods: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n = 30) and IDC (n = 30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. Results: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p < 0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p < 0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p < 0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p < 0.0001). Conclusions: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.

  9. Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

    Science.gov (United States)

    Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

    2016-02-01

    The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

  10. Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.

    Science.gov (United States)

    Truin, W; Vugts, G; Roumen, R M H; Maaskant-Braat, A J G; Nieuwenhuijzen, G A P; van der Heiden-van der Loo, M; Tjan-Heijnen, V C G; Voogd, A C

    2016-01-01

    This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC). Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry. A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC. The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

  11. Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks

    Science.gov (United States)

    Cruz-Roa, Angel; Basavanhally, Ajay; González, Fabio; Gilmore, Hannah; Feldman, Michael; Ganesan, Shridar; Shih, Natalie; Tomaszewski, John; Madabhushi, Anant

    2014-03-01

    This paper presents a deep learning approach for automatic detection and visual analysis of invasive ductal carcinoma (IDC) tissue regions in whole slide images (WSI) of breast cancer (BCa). Deep learning approaches are learn-from-data methods involving computational modeling of the learning process. This approach is similar to how human brain works using different interpretation levels or layers of most representative and useful features resulting into a hierarchical learned representation. These methods have been shown to outpace traditional approaches of most challenging problems in several areas such as speech recognition and object detection. Invasive breast cancer detection is a time consuming and challenging task primarily because it involves a pathologist scanning large swathes of benign regions to ultimately identify the areas of malignancy. Precise delineation of IDC in WSI is crucial to the subsequent estimation of grading tumor aggressiveness and predicting patient outcome. DL approaches are particularly adept at handling these types of problems, especially if a large number of samples are available for training, which would also ensure the generalizability of the learned features and classifier. The DL framework in this paper extends a number of convolutional neural networks (CNN) for visual semantic analysis of tumor regions for diagnosis support. The CNN is trained over a large amount of image patches (tissue regions) from WSI to learn a hierarchical part-based representation. The method was evaluated over a WSI dataset from 162 patients diagnosed with IDC. 113 slides were selected for training and 49 slides were held out for independent testing. Ground truth for quantitative evaluation was provided via expert delineation of the region of cancer by an expert pathologist on the digitized slides. The experimental evaluation was designed to measure classifier accuracy in detecting IDC tissue regions in WSI. Our method yielded the best quantitative

  12. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  13. Micro-PIXE analysis in invasive ductal carcinoma tissues after treatment of astaxanthin

    International Nuclear Information System (INIS)

    Safaverdi, S.; Roshani, F.; Lamehi Rashti, M.; Golkhoo, Sh.; Hassan, Z. M.; Langroudi, L.

    2009-01-01

    Trace elements play an important role in a number of biological processes. Astaxanthin, a carotoid pigment found in certain marine plant and animals, has shown anti cancer and anti free radical properties. This work intended to understand the effect of Astaxanthin in breast cancer (invasive ductal carcinoma) by using micro-PIXE method. For this aim the concentration of trace elements were compared in healthy, cancerous and cancer treated with astaxanthin in the breast and liver tissues of breast cancer bearing mice, using proton induced X-ray emission. Materials and Methods: Proton induced X-ray emission was used In a study intending to compare the concentration of trace elements in breast and liver tissues of mice bearing tumor, three groups of mice: healthy, cancerous, and cancerous treated by astaxanthin, were considered. Astaxanthin was supplied from Research Institute of women, Alzahra University. Results: Comparing the untreated tumor tissue, treatment with Astaxanthm significantly decreased the amount Fe, P, S, and Ca elements level in tumor tissue of the breast cancer. It is also found that the concentrations of those elements in liver of the untreated mice and the liver of treated mice with astaxanthin were fairly equal. Astaxanthln significantly decrease the accumulation of elements in the site of tumor, and caused the breast cancer cell membrane to lose their desire to collect the elements from healthy tissues. Conclusion: The micro -PIXE technique could calculate elemental concentrations in tissues. Changes in metallic elements may affect microenvironment and cell functions, which might led lead to cell degeneration or death, the results shows that astaxanthin reduces vital element concentration in tumor site, thus it could be used as an anti tumor agent.

  14. Comparison of the Subgross Distribution of the Lesions in Invasive Ductal and Lobular Carcinomas of the Breast: A Large-Format Histology Study

    Directory of Open Access Journals (Sweden)

    Syster Hofmeyer

    2012-01-01

    Full Text Available To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586, multifocal in 35.5% (208/586, and diffuse in 1.2% (7/586 of the cases. The corresponding figures in the lobular group were 27.8% (37/133, 45.9% (61/586, and 26.3% (35/133, respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586, multifocal in 31.6% (185/586, and diffuse in 26.8% (157/586 of the cases. The corresponding figures in the lobular category were 15.0% (20/133, 54.2% (72/133, and 30.8% (41/133, respectively. Ductal cancers were extensive in 45.7% (268/586, lobular in 65.4% (87/133 of the cases. All these differences were statistically highly significant (. While the histological tumor type itself (ductal versus lobular did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers.

  15. In Situ Malignant Transformation and Progenitor-Mediated Cell Budding: Two Different Pathways for Breast Ductal and Lobular Tumor Invasion

    Directory of Open Access Journals (Sweden)

    Yan-gao Man, Mina Izadjoo, Guohong Song, Alexander Stojadinovic

    2011-01-01

    Full Text Available The human breast lobular and ductal structures and the derived tumors from these structures differ substantial in their morphology, microenvironment, biological presentation, functions, and clinical prognosis. Based on these differences, we have proposed that pre-invasive lobular tumors may progress to invasive lesions through “in situ malignant transformation”, in which the entire myoepithelial cell layer within a given lobule or lobular clusters undergoes extensive degeneration and disruptions, which allows the entire epithelial cell population associated with these myoepithelial cell layers directly invade the stroma or vascular structures. In contrast, pre-invasive ductal tumors may invade the stroma or vascular structures through “progenitor-mediated cell budding”, in which focal myoepithelial cell degeneration-induced aberrant leukocyte infiltration causes focal disruptions in the tumor capsules, which selectively favor monoclonal proliferation of the overlying tumor stem cells or a biologically more aggressive cell clone. Our current study attempted to provide more direct morphological and immunohistochemical data that are consistent with our hypotheses.

  16. Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

    Science.gov (United States)

    Hamada, Yoshihiro; Nakayama, Yoshifuku

    Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    Energy Technology Data Exchange (ETDEWEB)

    Farquharson, M J [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St W Hamilton, Ontario, L8S 4L8 (Canada); Al-Ebraheem, A [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Geraki, K [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE (United Kingdom); Leek, R; Jubb, A; Harris, A L [Cancer Research UK, Oxford Cancer Centre, Molecular Oncology Laboratories, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, 0X3 9DS (United Kingdom)], E-mail: farquhm@mcmaster.ca

    2009-07-07

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01)

  18. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    International Nuclear Information System (INIS)

    Farquharson, M J; Al-Ebraheem, A; Geraki, K; Leek, R; Jubb, A; Harris, A L

    2009-01-01

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

  19. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    International Nuclear Information System (INIS)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee; Zeon, Seok Kil; Kim, Su Jin

    2015-01-01

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV max ) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV max of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV max compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer

  20. Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

    Science.gov (United States)

    Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

  1. The diagnosis and management of pre-invasive breast disease: Ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) – current definitions and classification

    International Nuclear Information System (INIS)

    Pinder, Sarah E; Ellis, Ian O

    2003-01-01

    Intraductal epithelial proliferations of the breast are at present classified into three groups; distinction is made histologically and clinically between usual epithelial hyperplasia and atypical ductal hyperplasia (ADH) and between ADH and ductal carcinoma in situ (DCIS). Although evidence indicates that these boundaries are not ideal on a morphological, immunohistochemical, or genetic basis, this three-tier system is accepted and used at present. The current definitions, histological features, and system of classification of ADH and DCIS are described in this manuscript

  2. Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: a 5-year experience with invasive ductal and lobular carcinomas.

    Science.gov (United States)

    Nassar, Aziza; Khoor, Andras; Radhakrishnan, Reshmitha; Radhakrishnan, Anu; Cohen, Cynthia

    2014-01-01

    The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.

  3. IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

    Science.gov (United States)

    Zhao, Huan-Yu; Han, Yang; Wang, Jian; Yang, Lian-He; Zheng, Xiao-Ying; Du, Jiang; Wu, Guang-Ping; Wang, En-Hua

    2017-06-01

    IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

  4. Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

    NARCIS (Netherlands)

    Hartog, Hermien; Horlings, Hugo M; van der Vegt, Bert; Kreike, Bas; Ajouaou, Abderrahim; van de Vijver, Marc J; Boezen, Hendrika; de Bock, Geertruida H; van der Graaf, Wilhelmina; Wesseling, Jelle

    2011-01-01

    The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast

  5. Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings

    NARCIS (Netherlands)

    El Sharouni, Mary Ann; Postma, Emily L.; van Diest, Paul J.

    2017-01-01

    Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy,

  6. Prospective Clinical Trial of 18F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers.

    Science.gov (United States)

    Ulaner, Gary A; Goldman, Debra A; Corben, Adriana; Lyashchenko, Serge K; Gönen, Mithat; Lewis, Jason S; Dickler, Maura

    2017-07-01

    18 F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ( 18 F-fluciclovine) is a leucine analog radiotracer that depicts amino acid transport into cells. 18 F-fluciclovine PET/CT visualizes malignancy, including prostate cancer, invasive ductal breast cancer, and invasive lobular breast cancer. Whether changes in 18 F-fluciclovine avidity reflect changes in tumor burden resulting from treatment has not been shown. In this prospective clinical trial (clinical trials.gov: NCT01864083), changes in 18 F-fluciclovine avidity after neoadjuvant therapy were compared to breast cancer therapy response, as determined by residual tumor burden on pathology, were evaluated. Methods: Twenty-four women with a new diagnosis of locally advanced invasive ductal breast cancer ( n = 18) or invasive lobular breast cancer ( n = 6) underwent 18 F-fluciclovine PET/CT before and after the completion of neoadjuvant systemic therapy. SUV max , SUV mean , metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes on each examination and corrected for background 18 F-fluciclovine avidity. The relationship between changes in 18 F-fluciclovine avidity and the percentage of reduction of tumor on pathology was assessed with the Spearman rank correlation. Results: The median decrease in the corrected SUV max of the primary breast lesions was 99% (range, 33%-100%). The median reduction of tumor on pathology was 92% (range, 10%-100%). Changes in 18 F-fluciclovine avidity were strongly correlated with the percentage of reduction of tumor on pathology (Spearman ρ, 0.79; 95% CI, 0.56-0.90; P < 0.001). Conclusion: Changes in 18 F-fluciclovine avidity strongly correlated with the tumor response on pathology in this pilot study. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  7. Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery

    DEFF Research Database (Denmark)

    Langhans, Linnea; Jensen, Maj-Britt; Talman, Maj-Lis M

    2017-01-01

    Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs...... to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS......) and to examine whether the risk of reoperation is associated with DCIS or histologic type of the IBC. Design, Setting, and Participants: This nationwide study including women with histologically verified IBC or DCIS having wire-guided BCS performed between January 1, 2010, and December 31, 2013, used data from...

  8. Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data.

    Science.gov (United States)

    Hirth, Jacqueline M; Hatch, Sandra S; Lin, Yu-Li; Giordano, Sharon H; Silva, H Colleen; Kuo, Yong-Fang

    2018-04-18

    Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data. This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample. In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower. DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  9. Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

    Science.gov (United States)

    Shi, Bibo; Hou, Rui; Mazurowski, Maciej A.; Grimm, Lars J.; Ren, Yinhao; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2018-02-01

    Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

  10. Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

    Directory of Open Access Journals (Sweden)

    Srovnal Josef

    2007-03-01

    Full Text Available Abstract Background Invasive ductal and lobular carcinomas (IDC and ILC are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. Methods We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17 was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Results Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1 distinguished large sets of IDC from ILC. Conclusion IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN and collagen triple helix repeat containing 1 (CTHRC1 which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue

  11. Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

    International Nuclear Information System (INIS)

    Turashvili, Gulisa; Srovnal, Josef; Hajduch, Marian; Murray, Paul; Kolar, Zdenek; Bouchal, Jan; Baumforth, Karl; Wei, Wenbin; Dziechciarkova, Marta; Ehrmann, Jiri; Klein, Jiri; Fridman, Eduard; Skarda, Jozef

    2007-01-01

    Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel

  12. Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival.

    Science.gov (United States)

    García-Fernández, Antonio; Lain, Josep María; Chabrera, Carol; García Font, Marc; Fraile, Manel; Barco, Israel; Torras, Merçe; Reñe, Asumpta; González, Sonia; González, Clarissa; Piqueras, Mercedes; Veloso, Enrique; Cirera, Lluís; Pessarrodona, Antoni; Giménez, Nuria

    2015-01-01

    Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow-up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re-excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease-free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology. © 2015 Wiley Periodicals, Inc.

  13. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  14. Sentinel Lymph Node Biopsy and Isolated Tumor Cells in Invasive Lobular Versus Ductal Breast Cancer

    NARCIS (Netherlands)

    Truin, Wilfred; Roumen, Rudi M.; Siesling, Sabine; van der Heiden-van der Loo, Margriet; Lobbezoo, Dorien J.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    2016-01-01

    Background Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in invasive breast cancer. The introduction of SLN biopsy with an extensive pathology examination, in addition to the introduction of the 2002 TNM classification, led to different axillary classification

  15. Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.

    Science.gov (United States)

    El-Naby, Noha Ed Hassab; Hassan Mohamed, Hameda; Mohamed Goda, Asmaa; El Sayed Mohamed, Ahmed

    2017-06-01

    A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature. We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center. This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls. Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003. Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  16. Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships

    International Nuclear Information System (INIS)

    Park, Kwang-Hwa; Choi, Sung-E; Eom, Minseob; Kang, Yup

    2005-01-01

    The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity, which is required for the ubiquitination of securin and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC activation is prevented. In addition, several APC-targeting molecules such as securin, polo-like kinase, aurora kinase, and SnoN have been reported to be oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis. However, the clinical significance and the involvement of APC in tumorigenesis have not been investigated. The expression of APC7 was immunohistochemically investigated in 108 invasive ductal carcinomas of the breast and its relationship with clinicopathologic parameters was examined. The expression of APC7 was defined as positive when the summed scores of staining intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+. Positive APC7 expression was less frequent than its negative expression when histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P = 0.0016) was elevated. The frequency of APC7 negative expression was higher in high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups. These data show that loss of APC7 expression is more common in breast carcinoma cases with poor prognostic parameters or malignant characteristics. They therefore suggest that dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer

  17. Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.

    Science.gov (United States)

    Park, Cheol Keun; Jung, Woo Hee; Koo, Ja Seung

    2016-08-01

    Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.

  18. Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ - A nested case-control study.

    Science.gov (United States)

    Visser, Lindy L; Elshof, Lotte E; Schaapveld, Michael; Van de Vijver, Koen; Groen, Emma J; Almekinders, Mathilde M; Bierman, Carolien; Van Leeuwen, Flora E; Rutgers, Emiel J T; Schmidt, Marjanka K; Lips, Esther H; Wesseling, Jelle

    2018-04-23

    Ductal carcinoma in situ (DCIS) is treated to prevent progression to invasive breast cancer. Yet, most lesions will never progress, implying that overtreatment exists. Therefore, we aimed to identify factors distinguishing harmless from potentially hazardous DCIS using a nested case-control study. We conducted a case-control study nested in a population-based cohort of DCIS patients treated with breast conserving surgery (BCS) alone (n=2,658) between 1989-2005. We compared clinical, pathological, and immunohistochemical DCIS characteristics of 200 women who subsequently developed ipsilateral invasive breast cancer (iIBC; cases) and 474 women who did not (controls), in a matched setting. Median follow-up time was 12.0 years (interquartile range 9.0-15.3). Conditional logistic regression models, were used to assess associations of various factors with subsequent iIBC risk after primary DCIS. High COX-2 protein expression showed the strongest association with subsequent iIBC (odds ratio [OR]=2.97, 95% confidence interval [95%CI] 1.72-5.10). In addition, HER2 overexpression (OR=1.56, 95%CI 1.05-2.31) and presence of periductal fibrosis (OR=1.44, 95%CI 1.01-2.06) were associated with subsequent iIBC risk. Patients with HER2+/COX-2high DCIS had a 4-fold higher risk of subsequent iIBC (vs. HER2-/COX-2low DCIS), and an estimated 22.8% cumulative risk of developing subsequent iIBC at 15 years. With this unbiased study design and representative group of DCIS patients treated by BCS alone, COX-2, HER2, and periductal fibrosis were revealed as promising markers predicting progression of DCIS into iIBC. Validation will be done in independent data sets. Ultimately, this will aid individual risk stratification of women with primary DCIS. Copyright ©2018, American Association for Cancer Research.

  19. The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

    Science.gov (United States)

    Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

    2014-07-01

    Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Directory of Open Access Journals (Sweden)

    Eline Boghaert

    2014-12-01

    Full Text Available Ductal carcinoma in situ (DCIS is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo, but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  1. Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

    Science.gov (United States)

    Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

    2014-12-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

  2. Development and evaluation of a prediction model for underestimated invasive breast cancer in women with ductal carcinoma in situ at stereotactic large core needle biopsy.

    Directory of Open Access Journals (Sweden)

    Suzanne C E Diepstraten

    Full Text Available BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. RESULTS: 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7% patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28, number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01, presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77, and microinvasion (OR 3.75, 95% CI 1.42-9.87. The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R(2, mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73, and fairly good calibration. CONCLUSION: The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.

  3. Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

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    Wen-Biao Shi

    Full Text Available Invasive micropapillary carcinoma (IMPC of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.A total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC cases were included. The clinical features, breast cancer-specific survival (BCSS and recurrence/metastasis-free survival (RFS of the patients were compared between these two groups.The IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively than patients with IDC (89.5% and 84.5%, respectively. Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%. In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034. A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001. However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.In Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

  4. Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

    Science.gov (United States)

    Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

    2013-02-01

    This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P normal areas (P = 0.054). There was a significant difference in MVC observed in all areas except for DCIS and FCD ± DIN (P < 0.001). We noted significant inverse correlations between MVC, HER2 expression, and the numbers of involved lymph nodes in invasive cancer and DCIS (P < 0.001). Most MVC were present in grade I, with the least frequent observed in grade III cases in the stroma of invasive cancer, DCIS and FCD ± DIN (P < 0.001).  Angiogenesis can be observed before any significant myofibroblastic changes in the pre-invasive breast lesions. The elevated content of myofibroblasts in stroma of tumor; probably may be a worse prognostic factor  and the steps from atypical epithelial hyperplasia to DCIS and then to the invasive carcinoma do not appear to be always part of a linear progression.

  5. Comparison of histological size at the time of diagnosis of invasive nonpalpable ductal and lobular breast cancers

    International Nuclear Information System (INIS)

    Perez-Aznar, J. M.; Garcia-Laborda, E.; Guzman de Villoria, J. A.

    2002-01-01

    To determine if there are differences in the mean histological sizes at the time of diagnosis between infiltrating ductal carcinomas (IDC) and infiltrating lobular carcinomas (ILC) of the breast. The distribution of the two histological types was compared by grouping tumor size in intervals according to the pTNM classification. We has a series of 900 consecutive non-palpable lesions suggestive of malignancy in the mammography of women undergoing annual screening. All lesions were marked by sterotaxis statistical study was made with the SPSS-X statisdics application. The data of 254 pure IDC and 24 pure ILC were obtained. The mean tumor size of the IDC was 12.o mm (SD=0.58). The mean size of the ILC was 15.7 mm (SD=1.28). There was no significant difference between them (p=0.179). No differences were found in the pTNM distribution between the two groups even after segmenting pT1 into T1a. T1b and T1c. Although it is accepted that ILC entails more clinical-radiological diagnostic difficulty, most authors find no differences in tumor size between ILC and other invasive carcinomas. The tumor size of our series was smaller than that of other authors who included palpable and non-palpable carcinomas in their series. The small number of cases of ILC was a study limitation. In our series, although the tumor size of ILC was somewhat larger, the difference was not statistically significant. (Author) 21 refs

  6. Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast

    International Nuclear Information System (INIS)

    Prasad, Chandra P; Rath, Gayatri; Mathur, Sandeep; Bhatnagar, Dinesh; Parshad, Rajinder; Ralhan, Ranju

    2009-01-01

    Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast. In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast. Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear β-catenin (p = 0.001), and cytoplasmic β-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression. The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells

  7. Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Chandra P [Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi (India); Department of Biochemistry, All India Institute of Medical Sciences, New Delhi (India); Rath, Gayatri [Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi (India); Mathur, Sandeep [Department of Pathology, All India Institute of Medical Sciences, New Delhi (India); Bhatnagar, Dinesh [Department of Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Dehi (India); Parshad, Rajinder [Department of Surgery, All India Institute of Medical Sciences, New Delhi -110029 (India); Ralhan, Ranju [Department of Biochemistry, All India Institute of Medical Sciences, New Delhi (India); Sonshine Family Centre for Head & Neck Disease, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5 (Canada); Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5 (Canada); Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5 (Canada); Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, M5G 2N2 (Canada)

    2009-09-14

    Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast. In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast. Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear β-catenin (p = 0.001), and cytoplasmic β-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression. The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells.

  8. Feasibility of the Less Is More Approach in Treating Low-Risk Ductal Carcinoma In Situ Diagnosed on Core Needle Biopsy: Ten-Year Review of Ductal Carcinoma In Situ Upgraded to Invasion at Surgery.

    Science.gov (United States)

    Podoll, Mirna B; Reisenbichler, Emily S; Roland, Lania; Bruner, Andrew; Mizuguchi, Sarah; Sanders, Mary Ann G

    2018-03-27

    - Ductal carcinoma in situ (DCIS) represents 20% of screen-detected breast cancers. The likelihood that certain types of DCIS are slow growing and may never progress to invasion suggests that our current standards of treating DCIS could result in overtreatment. The LORIS (LOw RISk DCIS) and LORD (LOw Risk DCIS) trials address these concerns by randomizing patients with low-risk DCIS to either active surveillance or conventional treatment. - To determine the upgrade rate of DCIS diagnosed on core needle biopsy to invasive carcinoma at surgery and to evaluate the safety of managing low-risk DCIS with surveillance alone, by characterizing the pathologic and clinical features of upgraded cases and applying criteria of the LORD and LORIS trials to these cases. - A 10-year retrospective analysis of DCIS on core needle biopsy with subsequent surgery. - We identified 1271 cases of DCIS on core needle biopsy: 200 (16%) low grade, 649 (51%) intermediate grade, and 422 (33%) high grade. Of the 1271 cases, we found an 8% upgrade rate to invasive carcinoma (n = 105). Nineteen of the 105 upgraded cases (18%) had positive lymph nodes. Low-grade DCIS was least likely to upgrade to invasion, comprising 10% (10 of 105) of upgraded cases. Three of the 105 upgraded cases (3%) met criteria for the LORD trial, and all were low-grade DCIS on core needle biopsy with favorable biology on follow-up. - There is a clear risk of upgrade to invasion on follow-up excision; however, applying strict criteria of the LORD trial effectively decreases the likelihood of a missed invasive component or missed aggressive pathologic features.

  9. The role of breast MR imaging in pre-operative determination of invasive disease for ductal carcinoma in situ diagnosed by needle biopsy

    International Nuclear Information System (INIS)

    Goto, Mariko; Yuen, Sachiko; Akazawa, Kentaro; Nishida, Kaori; Yamada, Kei; Konishi, Eiichi; Kajihara, Mariko; Shinkura, Nobuhiko

    2012-01-01

    To evaluate whether magnetic resonance (MR) imaging features can predict the presence of occult invasion in cases of biopsy-proven pure ductal carcinoma in situ (DCIS). We retrospectively reviewed 92 biopsy-proven pure DCIS in 92 women who underwent MR imaging. The following MR imaging findings were compared between confirmed DCIS and invasive breast cancer (IBC): lesion size, type, morphological and kinetic assessments by ACR BI-RADS MRI, and findings of fat-suppressed T2-weighted (FS-T2W) imaging. Sixty-eight of 92 (74%) were non-mass-like enhancements (NMLE) and 24 were mass lesions on MR imaging. Twenty-one of 68 (31%) NMLE and 13 of 24 (54%) mass lesions were confirmed as IBC. In NMLE lesions, large lesions (P = 0.007) and higher signal intensities (SI) on FS-T2W images (P = 0.032) were significantly associated with IBC. Lesion size remained a significant independent predictor of invasion in multivariate analysis (P = 0.032), and combined with FS-T2W SIs showed slightly higher observer performances (area under the curve, AUC, 0.71) than lesion size alone (AUC 0.68). There were no useful findings that enabled the differentiation of mass-type lesions. Breast MR imaging is potentially useful to predict the presence of occult invasion in biopsy-proven DCIS with NMLE. MR mammography permits more precise lesion assessment including ductal carcinoma in situ A correct diagnosis of occult invasion before treatment is important for clinicians This study showed the potential of MR mammography to diagnose occult invasion Treatment and/or aggressive biopsy can be given with greater confidence MR mammography can lead to more appropriate management of patients. (orig.)

  10. Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

    Science.gov (United States)

    Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

    2011-10-01

    The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

  11. Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Povoski Stephen P

    2009-03-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC versus that of invasive ductal carcinoma (IDC has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Methods We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed. Results No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385, specificity (100% vs. 100%, accuracy (86% vs. 92%, P = 0.172, false negative rate (33% vs. 25%, P = 0.385, negative predictive value (81% vs. 89%, P = 0.158, and positive predictive value (100% vs. 100% for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Conclusion Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis

  12. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27.

    Science.gov (United States)

    Strasser-Weippl, K; Sudan, G; Ramjeesingh, R; Shepherd, L E; O'Shaughnessy, J; Parulekar, W R; Liedke, P E R; Chen, B E; Goss, P E

    2018-02-01

    Histological subtype, (invasive ductal breast cancer (IDBC)/invasive lobular breast cancer (ILBC)), might be a marker for differential response to endocrine therapy in breast cancer. Clinical trial MA.27 compared 5 years of adjuvant anastrozole or exemestane in postmenopausal patients with hormone receptor positive early breast cancer. We evaluated IDBC versus ILBC (based on original pathology reports) as predictor for event-free survival (EFS) and overall survival (OS). A total of 5709 patients (5021 with IDBC and 688 with ILBC) were included (1876 were excluded because of missing or other histological subtype). Median follow-up was 4.1 years. Overall, histological subtype did not influence OS or EFS (HR (hazard ratio) 1.14, 95% confidence interval (CI) [0.79-1.63], P = 0.49 and HR 1.04, 95% CI [0.77-1.41], P = 0.81, respectively). There was no significant difference in OS between treatment with exemestane versus treatment with anastrozole in the IDBC group (HR = 0.92, 95% CI [0.73-1.16], P = 0.46). In the ILBC group, a marginally significant difference in favour of treatment with anastrozole was seen (HR = 1.79, 95% CI [0.98-3.27], P = 0.055). In multivariable analysis a prognostic effect of the interaction between treatment and histological subtype on OS (but not on EFS) was noted, suggesting a better outcome for patients with ILBC on anastrozole (HR 2.1, 95% CI [0.99-4.29], P = 0.05). After stepwise selection in the multivariable model, a marginally significant prognostic effect for the interaction variable (treatment with histological subtype) on OS (but not on EFS) was noted (Ratio of HR 2.1, 95% CI [1.00-4.31], P = 0.05). Our data suggest an interaction effect between treatment and histology (P = 0.05) on OS. Here, patients with ILBC cancers had a better OS when treated with anastrozole versus exemestane, whereas no difference was noted for patients with IDBC. NCT00066573. Crown Copyright © 2017. Published by Elsevier Ltd. All rights

  13. A Simple Model to Assess the Probability of Invasion in Ductal Carcinoma In Situ of the Breast Diagnosed by Needle Biopsy

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    Oldřich Coufal

    2014-01-01

    Full Text Available Objectives. The aim of the study was to develop a clinical prediction model for assessing the probability of having invasive cancer in the definitive surgical resection specimen in patients with biopsy diagnosis of ductal carcinoma in situ (DCIS of the breast, to facilitate decision making regarding axillary surgery. Methods. In 349 women with DCIS, predictors of invasion in the definitive resection specimen were identified. A model to predict the probability of invasion was developed and subsequently simplified to divide patients into two risk categories. The model’s performance was validated on another patient population. Results. Multivariate logistic regression revealed four independent predictors of invasion: (i suspicious (microinvasion in the biopsy specimen; (ii visibility of the lesion on ultrasonography; (iii size of the lesion on mammography >30 mm; (iv clinical palpability of the lesion. The actual frequency of invasion in the high-risk patient group in the test and validation population was 52.6% and 48.3%, respectively; in the low-risk group it was 16.8% and 7.1%, respectively. Conclusion. The model proved to have good performance. In patients with a low probability of invasion, an axillary procedure can be omitted without a substantial risk of additional surgery.

  14. Lactobacillus casei ssp.casei induced Th1 cytokine profile and natural killer cells activity in invasive ductal carcinoma bearing mice.

    Science.gov (United States)

    Soltan Dallal, Mohammad Mehdi; Yazdi, Mohammad Hossein; Holakuyee, Marzieh; Hassan, Zuhair Mohammad; Abolhassani, Mohsen; Mahdavi, Mehdi

    2012-06-01

    Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (Psurvival was significantly prolonged in comparison to the controls. Our findings suggest that daily intake of L.casei can improve immune responses in mice bearing invasive ductal carcinoma, but further studies are needed to investigate the other involving mechanisms in this case.

  15. Deep learning-based features of breast MRI for prediction of occult invasive disease following a diagnosis of ductal carcinoma in situ: preliminary data

    Science.gov (United States)

    Zhu, Zhe; Harowicz, Michael; Zhang, Jun; Saha, Ashirbani; Grimm, Lars J.; Hwang, Shelley; Mazurowski, Maciej A.

    2018-02-01

    Approximately 25% of patients with ductal carcinoma in situ (DCIS) diagnosed from core needle biopsy are subsequently upstaged to invasive cancer at surgical excision. Identifying patients with occult invasive disease is important as it changes treatment and precludes enrollment in active surveillance for DCIS. In this study, we investigated upstaging of DCIS to invasive disease using deep features. While deep neural networks require large amounts of training data, the available data to predict DCIS upstaging is sparse and thus directly training a neural network is unlikely to be successful. In this work, a pre-trained neural network is used as a feature extractor and a support vector machine (SVM) is trained on the extracted features. We used the dynamic contrast-enhanced (DCE) MRIs of patients at our institution from January 1, 2000, through March 23, 2014 who underwent MRI following a diagnosis of DCIS. Among the 131 DCIS patients, there were 35 patients who were upstaged to invasive cancer. Area under the ROC curve within the 10-fold cross-validation scheme was used for validation of our predictive model. The use of deep features was able to achieve an AUC of 0.68 (95% CI: 0.56-0.78) to predict occult invasive disease. This preliminary work demonstrates the promise of deep features to predict surgical upstaging following a diagnosis of DCIS.

  16. Initial Results of a Prospective Clinical Trial of 18F-Fluciclovine PET/CT in Newly Diagnosed Invasive Ductal and Invasive Lobular Breast Cancers.

    Science.gov (United States)

    Ulaner, Gary A; Goldman, Debra A; Gönen, Mithat; Pham, Hanh; Castillo, Raychel; Lyashchenko, Serge K; Lewis, Jason S; Dang, Chau

    2016-09-01

    (18)F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a leucine analog PET/CT radiotracer that depicts amino acid transport into cells. Amino acid transport proteins have been shown to be upregulated in breast malignancies by microarray and immunohistochemical analysis, so we hypothesized that (18)F-fluciclovine may provide a novel method of visualizing breast cancer and now report a prospective clinical trial of (18)F-fluciclovine PET/CT in newly diagnosed advanced local invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Twenty-seven women with a new diagnosis of locally advanced IDC (n = 19) or ILC (n = 8) underwent PET/CT of the chest after intravenous administration of 370 MBq of (18)F-fluciclovine. The SUVmax, SUVmean, metabolic tumor volume, and total lesion avidity were obtained for the primary breast tumor, axillary lymph nodes, and extraaxillary lymph nodes. Sites of previously unsuspected malignancy were recorded and confirmed by pathology. Results of (18)F-fluciclovine PET/CT were compared with those of (18)F-FDG PET/CT, when available, using the concordance correlation coefficient. All locally advanced breast cancers were (18)F-fluciclovine-avid. Of 21 patients with pathologically proven axillary nodal metastases, (18)F-fluciclovine-avid axillary nodes were seen in 20. (18)F-fluciclovine detected pathologically proven extraaxillary nodal metastases in 3 patients, including 2 previously unsuspected internal mammary nodes. Fourteen patients underwent (18)F-FDG PET/CT for comparison with (18)F-fluciclovine. Concordance for metabolic tumor volume between (18)F-fluciclovine and (18)F-FDG was strong (concordance correlation coefficient, 0.89; 95% confidence interval, 0.73-0.96), but concordance for SUVmax was weak (concordance correlation coefficient, 0.04; 95% confidence interval, -0.16-0.24). In patients with both modalities available (n = 14), primary ILCs (n = 4) demonstrated (18)F-fluciclovine avidity

  17. Staging performance of whole-body DWI, PET/CT and PET/MRI in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Catalano, Onofrio Antonio; Daye, Dania; Signore, Alberto; Iannace, Carlo; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Filomena, Mazzeo; Mansi, Luigi; Soricelli, Andrea; Salvatore, Marco; Fuin, Niccolo; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

    2017-07-01

    The aim of the present study was to evaluate the performance of whole-body diffusion-weighted imaging (WB-DWI), whole-body positron emission tomography with computed tomography (WB-PET/CT), and whole-body positron emission tomography with magnetic resonance imaging (WB-PET/MRI) in staging patients with untreated invasive ductal carcinoma of the breast. Fifty-one women with newly diagnosed invasive ductal carcinoma of the breast underwent WB-DWI, WB-PET/CT and WB-PET/MRI before treatment. A radiologist and a nuclear medicine physician reviewed in consensus the images from the three modalities and searched for occurrence, number and location of metastases. Final staging, according to each technique, was compared. Pathology and imaging follow-up were used as the reference. WB-DWI, WB-PET/CT and WB-PET/MRI correctly and concordantly staged 33/51 patients: stage IIA in 7 patients, stage IIB in 8 patients, stage IIIC in 4 patients and stage IV in 14 patients. WB-DWI, WB-PET/CT and WB-PET/MRI incorrectly and concordantly staged 1/51 patient as stage IV instead of IIIA. Discordant staging was reported in 17/51 patients. WB-PET/MRI resulted in improved staging when compared to WB-PET/CT (50 correctly staged on WB-PET/MRI vs. 38 correctly staged on WB-PET/CT; McNemar's test; p<0.01). Comparing the performance of WB-PET/MRI and WB-DWI (43 correct) did not reveal a statistically significant difference (McNemar test, p=0.14). WB-PET/MRI is more accurate in the initial staging of breast cancer than WB-DWI and WB-PET/CT, however, the discrepancies between WB-PET/MRI and WB-DWI were not statistically significant. When available, WB-PET/MRI should be considered for staging patient with invasive ductal breast carcinoma.

  18. Immunohistochemical and Proteomic Evaluation of Nuclear Ubiquitous Casein and Cyclin-Dependent Kinases Substrate in Invasive Ductal Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Piotr Ziółkowski

    2009-01-01

    Full Text Available Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS is 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as structure of its DNA binding domain resembles that of high-mobility group A, HMGA proteins. HMGA proteins are associated with various malignancies. Since changes in expression of HMGA are considered as marker of tumor progression, it is possible that similar changes in expression of NUCKS could be useful tool in diagnosis and prognosis of breast cancer. For identification and analysis of NUCKS we used proteomic and histochemical methods. Analysis of patient-matched samples of normal and breast cancer by mass spectrometry revealed elevated levels of NUCKS in protein extracts from ductal breast cancers. We elicited specific antibodies against NUCKS and used them for immunohistochemistry in invasive ductal carcinoma of breast. We found high expression of NUCKS in 84.3% of cancer cells. We suggest that such overexpression of NUCKS can play significant role in breast cancer biology.

  19. Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

    Science.gov (United States)

    Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S

    2001-08-01

    Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

  20. Flat epithelial atypia and atypical ductal hyperplasia: carcinoma underestimation rate.

    Science.gov (United States)

    Ingegnoli, Anna; d'Aloia, Cecilia; Frattaruolo, Antonia; Pallavera, Lara; Martella, Eugenia; Crisi, Girolamo; Zompatori, Maurizio

    2010-01-01

    This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

  1. Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review.

    Science.gov (United States)

    Demoor-Goldschmidt, C; Mahé, M-A; Supiot, S

    2018-04-01

    Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  2. Tumor characteristics and the clinical outcome of invasive lobular carcinoma compared to infiltrating ductal carcinoma in a Chinese population

    Directory of Open Access Journals (Sweden)

    Cao A-Yong

    2012-07-01

    Full Text Available Abstract Background We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC using a large database. Methods Clinicopathologic features, overall survival (OS, and recurrence/metastasis-free survival (RFS were compared between 2,202 patients with IDC and 215 patients with ILC. Results ILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P =0.001. The frequencies of recurrence/metastasis (P = 0.980 and death (P = 0.064 were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months. Conclusions Chinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.

  3. Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings.

    Science.gov (United States)

    El Sharouni, Mary-Ann; Postma, Emily L; van Diest, Paul J

    2017-12-01

    Invasive breast cancer comprises a spectrum of histological changes with purely lobular cancer on one side and purely ductal cancer on the other, with many mixed lesions in between. In a previous study, we showed that in patients with any percentage lobular component at core needle biopsy, preoperative MRI leads to the detection of clinically relevant additional findings in a substantial percentage of patients, irrespective of the percentage of the lobular component. Detection of a small lobular component may however not be reproducible among pathologists. Loss of membrane expression of E-cadherin or p120 is useful biomarkers of ILC and may therefore support a more objective diagnosis. All patients diagnosed with breast cancer containing a lobular component of any percentage between January 2008 and October 2012 were prospectively offered preoperative MRI. Clinically relevant additional findings on MRI were verified by pathology evaluation. Expression patterns of E-cadherin and p120 were evaluated by immunohistochemistry on the core needle biopsy. MRI was performed in 109 patients. The percentage of lobular component was significantly increased in cases with aberrant E-cadherin or p120 expression (both p = lobular component in the core needle of their breast cancer.

  4. Risk of invasive breast cancer and ductal carcinoma in situ in women with atypical papillary lesions of the breast.

    Science.gov (United States)

    Cuneo, Kyle C; Dash, Rajesh C; Wilke, Lee G; Horton, Janet K; Koontz, Bridget F

    2012-09-01

    Benign papillary lesions of the breast include papilloma and papillomatosis. A retrospective analysis of patients with a papillary breast lesion diagnosed between October 1992 and December 2009 was performed. Patients were excluded if they had a previous or concurrent diagnosis of invasive or in situ cancer or less than 6 months of follow-up. The Kaplan-Meier method was used to determine the risk of developing subsequent malignancy. The log rank test was used to compare groups of patients. Median follow-up for the 167 patients included in the study was 4.6 years. Fifty-one patients had a papillary lesion with atypia and 116 patients had a papillary lesion without atypia. Patients with a papillary lesion with atypia were more likely to develop invasive or in situ breast cancer with a 5 year risk of 13.0% versus 4.6% in patients with no atypia (p = 0.03). © 2012 Wiley Periodicals, Inc.

  5. The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.

    Science.gov (United States)

    Surmacki, Jakub; Brozek-Pluska, Beata; Kordek, Radzislaw; Abramczyk, Halina

    2015-04-07

    Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.

  6. Prevalence and Correlation of Human Papilloma Virus and its Types with Prognostic Markers in Patients with Invasive Ductal Carcinoma of the Breast in Kuwait

    Science.gov (United States)

    Francis, Issam M.; Al-Ayadhy, Bushra; Al-Awadhi, Shafiqa; Kapila, Kusum; Al-Mulla, Fahd

    2013-01-01

    Objectives: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. Methods: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. Results: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. Conclusion: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected. PMID:24273662

  7. Prevalence and correlation of human papilloma virus and its types with prognostic markers in patients with invasive ductal carcinoma of the breast in kuwait.

    Science.gov (United States)

    Francis, Issam M; Al-Ayadhy, Bushra; Al-Awadhi, Shafiqa; Kapila, Kusum; Al-Mulla, Fahd

    2013-11-01

    This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected.

  8. Differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma and pancreatic ductal adenocarcinoma on ultrasonography: the utility of echo intensity and contrast enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Masato [Dept. of Radiology, Sapporo Teishinkai Hospital, Sapporo (Japan); Hirokawa, Naoki; Usami, Yoko; Someya, Masanori; Sakata, Kohichi [Dept. of Radiology, Sapporo Medical University School of Medicine, Sapporo (Japan)

    2017-07-15

    The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. This study included eight and 37 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors. In the quantitative echo intensity evaluation, the two groups were compared with respect to the difference between the tumor intensity and the pancreatic intensity (TI-PI) and between the tumor intensity and the vascular intensity (TI-VI). In the quantitative contrast enhancement evaluation, the increase in echo intensity (ΔTI) and increase in echo intensity per unit of time (slope) were compared between the groups. The echo intensity and contrast enhancement were also compared between the two groups in patients with T3-T4 disease. In addition, the correlations of the histological type, tumor size, stromal type, and T factor with echogenicity and contrast enhancement were analyzed. IPMN-IC had significantly greater echo intensity and contrast enhancement than PDAC (TI-PI, P=0.004; TI-VI, P=0.001; ΔTI, P=0.012; slope, P=0.002). In T3-T4 disease, IPMN-IC also showed greater echo intensity and faster enhancement than PDAC. Echo intensity and contrast enhancement were correlated with histological type (TI-PI, P=0.003; TI-VI, P<0.001; ΔTI, P=0.007; slope, P<0.001). IPMN-IC and PDAC can be differentiated by the quantitative evaluation of echo intensity and contrast enhancement.

  9. Triple negativity and young age as prognostic factors in lymph node-negative invasive ductal carcinoma of 1 cm or less

    International Nuclear Information System (INIS)

    Kwon, Ji Hyun; Kim, In-Ah; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Bang, Yung-Jue; Ha, Sung Whan; Kim, Yu Jung; Lee, Keun-Wook; Oh, Do-Youn; Park, So Yeon; Kim, Jee Hyun; Chie, Eui Kyu; Kim, Sung-Won; Im, Seock-Ah

    2010-01-01

    Whether a systemic adjuvant treatment is needed is an area of controversy in patients with node-negative early breast cancer with tumor size of ≤1 cm, including T1mic. We performed a retrospective analysis of clinical and pathology data of all consecutive patients with node-negative T1mic, T1a, and T1b invasive ductal carcinoma who received surgery between Jan 2000 and Dec 2006. The recurrence free survival (RFS) and risk factors for recurrence were identified. Out of 3889 patients diagnosed with breast cancer, 375 patients were enrolled (T1mic:120, T1a:93, T1b:162). Median age at diagnosis was 49. After a median follow up of 60.8 months, 12 patients developed recurrences (T1mic:4 (3.3%), T1a:2 (2.2%), T1b:6 (3.7%)), with a five-year cumulative RFS rate of 97.2%. Distant recurrence was identified in three patients. Age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) and triple negative disease (HR 4.93; 95% CI 1.312-18.519, p = 0.018) were significantly associated with a higher rate of recurrence. HER2 overexpression, Ki-67, and p53 status did not affect RFS. Prognosis of node-negative breast cancer with T1mic, T1a and T1b is excellent, but patients under 35 years of age or with triple negative disease have a relatively high risk of recurrence

  10. Genetic predisposition to ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    C. Petridis (Christos); R.H. Brook; V. Shah (Vandna); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); D. Levi (Dina); E. Papouli (Efterpi); N. Orr (Nick); A. Cox (Angela); S.S. Cross (Simon); I. dos Santos Silva (Isabel); J. Peto (Julian); A.J. Swerdlow (Anthony ); M. Schoemaker (Minouk); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); J. Benítez (Javier); A. González-Neira (Anna); D.C. Tessier (Daniel C.); D. Vincent (Daniel); J. Li (Jingmei); J.D. Figueroa (Jonine); V. Kristensen (Vessela); A.-L. Borresen-Dale (Anne-Lise); P. Soucy (Penny); J. Simard (Jacques); R.L. Milne (Roger); G.G. Giles (Graham); S. Margolin (Sara); A. Lindblom (Annika); T. Brüning (Thomas); H. Brauch (Hiltrud); M.C. Southey (Melissa); J.L. Hopper (John); T. Dörk (Thilo); N.V. Bogdanova (Natalia); M. Kabisch (Maria); U. Hamann (Ute); R.K. Schmutzler (Rita); A. Meindl (Alfons); H. Brenner (Hermann); V. Arndt (Volker); R. Winqvist (Robert); K. Pykäs (Katri); P.A. Fasching (Peter); M.W. Beckmann (Matthias); J. Lubinski (Jan); A. Jakubowska (Anna); A.M. Mulligan (Anna Marie); I.L. Andrulis (Irene); R.A.E.M. Tollenaar (Rob); P. Devilee (Peter); L. Le Marchand (Loic); C.A. Haiman (Christopher); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); P. Radice (Paolo); P. Peterlongo (Paolo); F. Marme (Federick); B. Burwinkel (Barbara); C.H.M. van Deurzen (Carolien); A. Hollestelle (Antoinette); N. Miller (Nicola); M. Kerin (Michael); D. Lambrechts (Diether); O.A.M. Floris; J. Wesseling (Jelle); H. Flyger (Henrik); S.E. Bojesen (Stig); S. Yao (Song); C.B. Ambrosone (Christine); G. Chenevix-Trench (Georgia); T. Truong (Thérèse); P. Guénel (Pascal); A. Rudolph (Anja); J. Chang-Claude (Jenny); H. Nevanlinna (Heli); C. Blomqvist (Carl); K. Czene (Kamila); J.S. Brand (Judith S.); J.E. Olson (Janet); F.J. Couch (Fergus); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); S. Pinder (Sarah); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); R. Roylance (Rebecca); M. García-Closas (Montserrat); E.J. Sawyer (Elinor)

    2016-01-01

    textabstractBackground: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk

  11. Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.

    Science.gov (United States)

    Wang, Tong; Ma, Yuanyuan; Wang, Liang; Liu, Hong; Chen, Meixuan; Niu, Ruifang

    2015-08-01

    The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.

  12. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  13. Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

    Science.gov (United States)

    Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

    2017-12-01

    There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors.

    Science.gov (United States)

    Autenshlyus, Alexander I; Arkhipov, Sergey A; Kunts, Tatiana A; Marinkin, Igor O; Mikhailova, Elena S; Karpukhina, Xenia V; Varaksin, Nikolay A

    2017-03-01

    Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = -0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = -0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.

  15. Ductal Carcinoma In Situ: The Whole Truth.

    Science.gov (United States)

    Parikh, Ujas; Chhor, Chloe M; Mercado, Cecilia L

    2018-02-01

    Ductal carcinoma in situ (DCIS) is a noninvasive malignant breast disease traditionally described as a precursor lesion to invasive breast cancer. With screening mammography, DCIS now accounts for approximately 20% of newly diagnosed cancer cases. DCIS is not well understood because of its heterogeneous nature. Studies have aimed to assess prognostic factors to characterize its risk of invasive potential; however, there still remains a lack of uniformity in workup and treatment. We summarize current knowledge of DCIS and the ongoing controversies.

  16. Evaluation of the R2* value in invasive ductal carcinoma with respect to hypoxic-related prognostic factors using iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL)

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Mari; Aoki, Takatoshi; Kinoshita, Shunsuke; Fujii, Masami; Korogi, Yukunori [University of Occupational and Environmental Health, Department of Radiology, Kitakyushu (Japan); Shimajiri, Shohei [University of Occupational and Environmental Health, Department of Pathology and Cell Biology, Kitakyushu (Japan); Matsuyama, Atsuji [University of Occupational and Environmental Health, Department of Pathology and Oncology, Kitakyushu (Japan); Katsuki, Takefumi; Inoue, Yuzuru [University of Occupational and Environmental Health, First Department of Surgery, Kitakyushu (Japan); Nagata, Yoshika; Tashima, Yuko [University of Occupational and Environmental Health, Second department of Surgery, Kitakyushu (Japan)

    2017-10-15

    To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma. Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α. FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001). Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma. (orig.)

  17. Upgrade of ductal carcinoma in situ on core biopsies to invasive disease at final surgery: a retrospective review across the Scottish Breast Screening Programme.

    Science.gov (United States)

    Sim, Y T; Litherland, J; Lindsay, E; Hendry, P; Brauer, K; Dobson, H; Cordiner, C; Gagliardi, T; Smart, L

    2015-05-01

    To identify factors affecting upgrade rates from B5a (non-invasive) preoperative core biopsies to invasive disease at surgery and ways to improve screening performance. This was a retrospective analysis of 1252 cases of B5a biopsies across all six Scottish Breast Screening Programmes (BSPs), ranging between 2004 and 2012. Final surgical histopathology was correlated with radiological and biopsy factors. Data were analysed using basic Microsoft Excel and standard Chi-squared test used for evaluating statistical significance. B5a upgrade rates for the units ranged from 19.2% to 29.2%, with an average of 23.6%. Mean sizes of invasive tumours were small (3-11 mm). The upgrade rate was significantly higher for cases where the main mammographic abnormality was mass, distortion, or asymmetry, compared with micro-calcification alone (33.2% versus 21.7%, p = 0.0004). The upgrade rate was significantly lower with the use of large-volume vacuum-assisted biopsy (VAB) devices than 14 G core needles (19.9% versus 26%, p = 0.013); in stereotactic than ultrasound-guided biopsies (21.2% versus 36.1%, p Scottish BSPs, including first-line biopsy technique and/or device; and it is of interest that a few centres maintain low upgrade rates despite not using VAB routinely for biopsy of micro-calcification. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  18. Upgrade of ductal carcinoma in situ on core biopsies to invasive disease at final surgery: a retrospective review across the Scottish Breast Screening Programme

    International Nuclear Information System (INIS)

    Sim, Y.T.; Litherland, J.; Lindsay, E.; Hendry, P.; Brauer, K.; Dobson, H.; Cordiner, C.; Gagliardi, T.; Smart, L.

    2015-01-01

    Aim: To identify factors affecting upgrade rates from B5a (non-invasive) preoperative core biopsies to invasive disease at surgery and ways to improve screening performance. Material and methods: This was a retrospective analysis of 1252 cases of B5a biopsies across all six Scottish Breast Screening Programmes (BSPs), ranging between 2004 and 2012. Final surgical histopathology was correlated with radiological and biopsy factors. Data were analysed using basic Microsoft Excel and standard Chi-squared test used for evaluating statistical significance. Results: B5a upgrade rates for the units ranged from 19.2% to 29.2%, with an average of 23.6%. Mean sizes of invasive tumours were small (3–11 mm). The upgrade rate was significantly higher for cases where the main mammographic abnormality was mass, distortion, or asymmetry, compared with micro-calcification alone (33.2% versus 21.7%, p = 0.0004). The upgrade rate was significantly lower with the use of large-volume vacuum-assisted biopsy (VAB) devices than 14 G core needles (19.9% versus 26%, p = 0.013); in stereotactic than ultrasound-guided biopsies (21.2% versus 36.1%, p < 0.001). Heterogeneity of data from different centres limited evaluation of other potential factors. Conclusion: Upgrade rates are lower for cases with micro-calcification as the sole mammographic feature with the use of VAB devices. Nevertheless, there is variation in practice across Scottish BSPs, including first-line biopsy technique and/or device; and it is of interest that a few centres maintain low upgrade rates despite not using VAB routinely for biopsy of micro-calcification. - Highlights: • Average B5a upgrade rate of 23.6% in our screening programme is comparable to published series. • Upgrade rate was lower in microcalcifications than non-calcific findings on mammography. • Upgrade rate was lower with use of vacuum-assisted biopsy devices than 14-gauge core needles

  19. High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Liu, Bingbing; Xiong, Jianhua; Liu, Guiqiu; Wu, Jing; Wen, Likun; Zhang, Qin; Zhang, Chuanshan

    2017-07-01

    The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (r s  = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a

  20. Lacrimal gland ductal carcinomas

    DEFF Research Database (Denmark)

    Andreasen, Simon; Grauslund, Morten; Heegaard, Steffen

    2017-01-01

    and xerophtalmia; case 2: A 53-year-old man, presented with headache, proptosis and chemosis and case 3: A 73-year-old man, presenting with chemosis and a corneal abscess. All three cases were characterized morphologically including immunohistochemistry and genetically with fluorescence in situ hybridization (FISH...... HER2 amplification was found in cases 2 and 3. CONCLUSION: This study identified a spectrum of genetic events and pattern of protein expression in DC of the lacrimal gland similar to a subset of carcinomas of the breast and ductal carcinomas of the salivary glands. For therapeutic purposes...

  1. Correlation of molecular subtypes of invasive ductal carcinoma of breast with glucose metabolism in FDG PET/CT: Based on the recommendations of the St. Gallen Consenesus Meeting 2013

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sang Kyun [Dept. of Nuclear Medicine, Haeundae Paik Hospital, University of Inje College of Medicine, Busan (Korea, Republic of); Lee, Sun Seong; Park, Yun Soo; Park, Ji Sun; Kim, Tae Hyun; Yoon, Hye Kyoung; Ahn, Hyo Jung; Lee, Seok Mo [Busan Paik Hospital, University of Inje College of Medicine, Busan (Korea, Republic of)

    2017-03-15

    This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013. Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUV{sub max} was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics. The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUV{sub max} in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUV{sub max} differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUV{sub max} to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively. The SUV{sub max} showed a significant correlation with the molecular subtype. Although SUV{sub max} measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUV{sub max}.

  2. Correlation of molecular subtypes of invasive ductal carcinoma of breast with glucose metabolism in FDG PET/CT: Based on the recommendations of the St. Gallen Consenesus Meeting 2013

    International Nuclear Information System (INIS)

    Bae, Sang Kyun; Lee, Sun Seong; Park, Yun Soo; Park, Ji Sun; Kim, Tae Hyun; Yoon, Hye Kyoung; Ahn, Hyo Jung; Lee, Seok Mo

    2017-01-01

    This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013. Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of the breast were reviewed. A total of 183 patients were included. SUV_m_a_x was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2-), luminal B-like HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics. The molecular subtype was LA in 38 patients, LBHER2- in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUV_m_a_x in the LA, LBHER2-, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUV_m_a_x differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUV_m_a_x to differentiate LA from LBHER2-, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively. The SUV_m_a_x showed a significant correlation with the molecular subtype. Although SUV_m_a_x measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUV_m_a_x

  3. Subareolar Sclerosing Ductal Hyperplasia.

    Science.gov (United States)

    Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

    2017-02-01

    Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

  4. Genetic predisposition to ductal carcinoma in situ of the breast

    DEFF Research Database (Denmark)

    Petridis, Christos; Brook, Mark N; Shah, Vandna

    2016-01-01

    BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci...... %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen......, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67...

  5. The clinical behavior of mixed ductal/lobular carcinoma of the breast: a clinicopathologic analysis

    Directory of Open Access Journals (Sweden)

    Dunnington Gary

    2010-06-01

    Full Text Available Abstract Background To date, the clinical presentation and prognosis of mixed ductal/lobular mammary carcinomas has not been well studied, and little is known about the outcome of this entity. Thus, best management practices remain undetermined due to a dearth of knowledge on this topic. Methods In this paper, we present a clinicopathologic analysis of patients at our institution with this entity and compare them to age-matched controls with purely invasive ductal carcinoma (IDC and historical data from patients with purely lobular carcinoma and also stain-available tumor specimens for E-cadherin. We have obtained 100 cases of ductal and 50 cases of mixed ductal/lobular breast carcinoma. Results Clinically, the behavior of mixed ductal/lobular tumors seemed to demonstrate some important differences from their ductal counterparts, particularly a lower rate of metastatic spread but with a much higher rate of second primary breast cancers. Conclusions Our data suggests that mixed ductal/lobular carcinomas are a distinct clinicopathologic entity incorporating some features of both lobular and ductal carcinomas and representing a pleomorphic variant of IDC.

  6. Ductal carcinoma in situ of the breast: histological classification and genetic alterations

    NARCIS (Netherlands)

    van de Vijver, M. J.

    1998-01-01

    Ductal carcinoma in situ (DCIS) of the breast represents a proliferation of malignant epithelial cells within the ducts and lobules of the breast, without invasion through the basement membrane. It is believed that all invasive carcinomas are preceded by DCIS; however, it is not known what

  7. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    Science.gov (United States)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  8. Histopathological and clonal study of combined lobular and ductal carcinoma of the breast

    Science.gov (United States)

    Tazaki, Eri; Shishido-Hara, Yukiko; Mizutani, Natsuko; Nomura, Sachiyo; Isaka, Hirotsugu; Ito, Hiroki; Imi, Kentaro; Imoto, Shigeru; Kamma, Hiroshi

    2013-01-01

    Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways. PMID:23782331

  9. Primary infiltrating ductal carcinoma of the axillary breast with metastasis to the contralateral chest wall

    Directory of Open Access Journals (Sweden)

    Li-Min Sun

    2013-06-01

    Full Text Available Primary infiltrating ductal carcinoma of the axillary breast is rare and has a high frequency of lymph node (LN involvement. We report a woman with primary infiltrating ductal carcinoma arising from the right axillary breast with metastasis to the contralateral chest wall. Excisional biopsy of the left chest wall nodule and the right axillary mass was carried out and both showed invasive ductal carcinomas histologically. The lesion of the right axillary mass arose from the breast tissue, rather than the LN. Further surgery proved the right axillary LN metastasis. After further review, a primary infiltrating ductal carcinoma of the right axillary breast with metastasis to axillary LNs and contralateral chest wall was diagnosed. The patient also received chemotherapy and radiation and there was no evidence of tumor recurrence after treatment. The present report demonstrated a rare case with uncommon manifestation. Lesions of uncertain origin around the periphery of the breast should be suspected for breast carcinoma.

  10. Ductal carcinoma of the breast in the pacemaker generator's pocket.

    Science.gov (United States)

    Zonca, P; Herokova, J; Cambal, M; Jacobi, C A

    2009-01-01

    Authors present a case of a 78-year-old female patient with invasive ductal adenocarcinoma in the pacemaker, s pocket. A decubitus-like tumor had developed in this place, and has been missinterpretated as a benign lesion for 5 months. Diagnosis was done with a time delay. An excisional biopsy revealed annvasive ductal adenocarcinoma. The first step was the implantation of a new pacemaker generator performed on the opposite side. The second step was a modified radical mastectomy, according to Madden, and the removal of the originally implanted pacemaker generator. Radiotherapy and hormonal adjuvant therapy were applied after surgery. The patient was followed-up at an out-patient clinic, and died 25 months after diagnosis because of generalization of the disease (Fig. 2, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

  11. Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020).

    Science.gov (United States)

    Nakhlis, Faina; Gilmore, Lauren; Gelman, Rebecca; Bedrosian, Isabelle; Ludwig, Kandice; Hwang, E Shelley; Willey, Shawna; Hudis, Clifford; Iglehart, J Dirk; Lawler, Elizabeth; Ryabin, Nicole Y; Golshan, Mehra; Schnitt, Stuart J; King, Tari A

    2016-03-01

    Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB. Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations. A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3%; 95% confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1%; 95% CI 0.01-7) by central pathology review. In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3% by local pathology and 1% by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings.

  12. Ductal carcinoma of the parotid gland.

    Science.gov (United States)

    Eriksen, H E; Greisen, O; Hastrup, N

    1987-06-01

    A case of ductal carcinoma of the parotid gland is described. The medical literature contains only 13 previous reports on this kind of adenocarcinoma of the parotid gland. The tumour is characterized by its histologic resemblance to ductal carcinomas of the breast and prostate. The course of previously described cases suggests that this tumour has a highly aggressive biological behaviour.

  13. Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast: friends or foes?

    Science.gov (United States)

    Agahozo, Marie Colombe; Hammerl, Dora; Debets, Reno; Kok, Marleen; van Deurzen, Carolien H M

    2018-02-20

    In the past three decades, the detection rate of ductal carcinoma in situ of the breast has dramatically increased due to breast screening programs. As a consequence, about 20% of all breast cancer cases are detected in this early in situ stage. Some ductal carcinoma in situ cases will progress to invasive breast cancer, while other cases are likely to have an indolent biological behavior. The presence of tumor-infiltrating lymphocytes is seen as a promising prognostic and predictive marker in invasive breast cancer, mainly in HER2-positive and triple-negative subtypes. Here, we summarize the current understanding regarding immune infiltrates in invasive breast cancer and highlight recent observations regarding the presence and potential clinical significance of such immune infiltrates in patients with ductal carcinoma in situ. The presence of tumor-infiltrating lymphocytes, their numbers, composition, and potential relationship with genomic status will be discussed. Finally, we propose that a combination of genetic and immune markers may better stratify ductal carcinoma in situ subtypes with respect to tumor evolution.

  14. Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer.

    Science.gov (United States)

    Huang, Bo; Omoto, Yoko; Iwase, Hirotaka; Yamashita, Hiroko; Toyama, Tatsuya; Coombes, Raoul Charles; Filipovic, Aleksandra; Warner, Margaret; Gustafsson, Jan-Åke

    2014-02-04

    The role of estrogen receptor (ER) α as a target in treatment of breast cancer is clear, but those of ERβ1 and ERβ2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ERα was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ERβ. We found that whereas ductal cancer is a highly proliferative, ERα-positive, ERβ-negative disease, lobular cancer expresses both ERα and ERβ but with very few Ki67-positive cells. ERβ2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ERβ2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1α. ERβ2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERα nor ERβ was expressed, but in the high-grade lobular cancer ERβ was lost and ERα and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ERβ agonists in preventing in situ ductal cancers from becoming invasive.

  15. The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

    Science.gov (United States)

    Dupouy, Sandra; Viardot-Foucault, Véronique; Alifano, Marco; Souazé, Frédérique; Plu-Bureau, Geneviève; Chaouat, Marc; Lavaur, Anne; Hugol, Danielle; Gespach, Christian; Gompel, Anne; Forgez, Patricia

    2009-01-01

    The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

  16. Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary

    International Nuclear Information System (INIS)

    Langlands, F.; White, J.; Kearins, O.; Cheung, S.; Burns, R.; Horgan, K.; Sharma, N.; Dodwell, D.

    2016-01-01

    Aim: To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC). Materials and methods: Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998–2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases. Results: A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer. Conclusion: There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning

  17. The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Tille

    Full Text Available PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens, and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.

  18. Ultrasound findings and histological features of ductal carcinoma in situ detected by ultrasound examination alone

    OpenAIRE

    Izumori, Ayumi; Takebe, Koji; Sato, Akira

    2009-01-01

    Background With the increasing use of high-resolution ultrasound (US) examination, many breast carcinomas that cannot be identified by mammography (MMG) alone have been detected. Many of these carcinomas are ductal carcinoma in situ (DCIS) and small-sized invasive carcinomas. Until date, DCISs have often been described as palpable masses with calcifications on MMG, but what are the characteristics of DCISs that are detectable by US alone? Methods One hundred fifty cases with DCIS that we expe...

  19. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H.M.; Molenaar, I. Quintus; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G.J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  20. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole

    2014-01-01

    directly linked to the hallmarks of cancer. The results found by proteogenomic analysis of the 32 tumor antigens studied here, capture largely the same pathway irregularities as those elucidated from large-scale screening of genomics analyses, where several thousands of genes are often found......Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic....... Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature...

  1. Epithelial proliferation in small ducts of salivary cystadenoma resembling atypical ductal hyperplasia of breast.

    Science.gov (United States)

    Fahim, Lisa; Weinreb, Ilan; Alexander, Cherupushpam; Perez Ordoñez, Bayardo

    2008-09-01

    Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 x 2.5 x 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed "Roman bridges", epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.

  2. Ductal carcinoma in a multiple fibroadenoma: Diagnostic inaccuracies

    Directory of Open Access Journals (Sweden)

    Rao Shalinee

    2010-01-01

    Full Text Available We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

  3. Ductal carcinoma in a multiple fibroadenoma: diagnostic inaccuracies.

    Science.gov (United States)

    Rao, Shalinee; Latha, P Suvarna; Ravi, A; Thanka, J

    2010-01-01

    We present the diagnostic inaccuracies encountered in a case of multiple fibroadenoma with malignant transformation. A 30-year-old lady presented with lump in the right breast of one month duration which on clinical examination, X-ray mammogram, sonomammogram were suggestive of multiple fibroadenomas. Fine needle aspiration cytology of the largest lump revealed features of malignancy and a core biopsy showed pleomorphic cells that could not be categorized. Due to the clinical, radiological and pathological diagnostic ambiguity, lumpectomy was performed and frozen section showed features of only conventional fibroadenoma. Representative bits on routine processing showed only features of fibroadenoma. Hence, complete submission of all lumps was done, which revealed fibroadenoma with invasive ductal carcinoma in one. Patient underwent modified radical mastectomy which showed multiple fibroadenomas, focal fibrocystic disease with a focus of residual invasive tumor and metastatic deposit in one axillary lymph node. This case report highlights the diagnostic challenges in detecting malignancy in fibroadenoma and a need for extensive tissue sampling in multiple fibroadenomas to detect the rare occurrence of carcinoma.

  4. Cellular automaton simulation examining progenitor hierarchy structure effects on mammary ductal carcinoma in situ.

    Science.gov (United States)

    Bankhead, Armand; Magnuson, Nancy S; Heckendorn, Robert B

    2007-06-07

    A computer simulation is used to model ductal carcinoma in situ, a form of non-invasive breast cancer. The simulation uses known histological morphology, cell types, and stochastic cell proliferation to evolve tumorous growth within a duct. The ductal simulation is based on a hybrid cellular automaton design using genetic rules to determine each cell's behavior. The genetic rules are a mutable abstraction that demonstrate genetic heterogeneity in a population. Our goal was to examine the role (if any) that recently discovered mammary stem cell hierarchies play in genetic heterogeneity, DCIS initiation and aggressiveness. Results show that simpler progenitor hierarchies result in greater genetic heterogeneity and evolve DCIS significantly faster. However, the more complex progenitor hierarchy structure was able to sustain the rapid reproduction of a cancer cell population for longer periods of time.

  5. Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: Long-term oncologic outcomes after standard resection.

    Science.gov (United States)

    Sahakyan, Mushegh A; Kim, Song Cheol; Kleive, Dyre; Kazaryan, Airazat M; Song, Ki Byung; Ignjatovic, Dejan; Buanes, Trond; Røsok, Bård I; Labori, Knut Jørgen; Edwin, Bjørn

    2017-10-01

    Surgical resection is the only curative option in patients with pancreatic ductal adenocarcinoma. Little is known about the oncologic outcomes of laparoscopic distal pancreatectomy. This bi-institutional study aimed to examine the long-term oncologic results of standard laparoscopic distal pancreatectomy in a large cohort of patients with pancreatic ductal adenocarcinoma. From January 2002 to March 2016, 207 patients underwent standard laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma at Oslo University Hospital-Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, Republic of Korea). After the exclusion criteria were applied (distant metastases at operation, conversion to an open operation, loss to follow-up), 186 patients were eligible for the analysis. Perioperative and oncologic variables were analyzed for association with recurrence and survival. Median overall and recurrence-free survivals were 32 and 16 months, while 5-year overall and recurrence-free survival rates were estimated to be 38.2% and 35.9%, respectively. Ninety-six (52%) patients developed recurrence: 56 (30%) extrapancreatic, 27 (15%) locoregional, and 13 (7%) combined locoregional and extrapancreatic. Thirty-seven (19.9%) patients had early recurrence (within 6 months of operation). In the multivariable analysis, tumor size >3 cm and no adjuvant chemotherapy were associated with early recurrence (P = .017 and P = .015, respectively). The Cox regression model showed that tumor size >3 cm and lymphovascular invasion were independent predictors of decreased recurrence-free and overall survival. Standard laparoscopic distal pancreatectomy is associated with satisfactory long-term oncologic outcomes in patients with pancreatic ductal adenocarcinoma. Several risk factors, such as tumor size >3 cm, no adjuvant chemotherapy, and lymphovascular invasion, are linked to poor prognosis after standard laparoscopic distal pancreatectomy. Copyright © 2017 Elsevier Inc

  6. Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

    Science.gov (United States)

    Grimm, Lars J; Ghate, Sujata V; Hwang, E Shelley; Soo, Mary Scott

    2017-11-01

    The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS). We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded. In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications. Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  7. Imaging features of ductal plate malformations in adults

    Energy Technology Data Exchange (ETDEWEB)

    Venkatanarasimha, N., E-mail: nandashettykv@yahoo.com [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom); Thomas, R.; Armstrong, E.M.; Shirley, J.F.; Fox, B.M.; Jackson, S.A. [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Ductal plate malformations, also known as fibrocystic liver diseases, are a group of congenital disorders resulting from abnormal embryogenesis of the biliary ductal system. The abnormalities include choledochal cyst, Caroli's disease and Caroli's syndrome, adult autosomal dominant polycystic liver disease, and biliary hamartoma. The hepatic lesions can be associated with renal anomalies such as autosomal recessive polycystic kidney disease (ARPKD), medullary sponge kidney, and nephronophthisis. A clear knowledge of the embryology and pathogenesis of the ductal plate is central to the understanding of the characteristic imaging appearances of these complex disorders. Accurate diagnosis of ductal plate malformations is important to direct appropriate clinical management and prevent misdiagnosis.

  8. Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load

    Directory of Open Access Journals (Sweden)

    Peter eHegyi

    2011-07-01

    Full Text Available Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel, however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.

  9. SMAD4 regulates cell motility through transcription of N-cadherin in human pancreatic ductal epithelium.

    Directory of Open Access Journals (Sweden)

    Ya'an Kang

    Full Text Available Expression of the cellular adhesion protein N-cadherin is a critical event during epithelial-mesenchymal transition (EMT. The SMAD4 protein has been identified as a mediator of transforming growth factor-β (TGF-β superfamily signaling, which regulates EMT, but the mechanisms linking TGF-β signaling to N-cadherin expression remain unclear. When the TGF-β pathway is activated, SMAD proteins, including the common mediator SMAD4, are subsequently translocated into the nucleus, where they influence gene transcription via SMAD binding elements (SBEs. Here we describe a mechanism for control of CDH2, the gene encoding N-cadherin, through the canonical TGFβ-SMAD4 pathway. We first identified four previously undescribed SBEs within the CDH2 promoter. Using telomerase immortalized human pancreatic ductal epithelium, we found that TGF-β stimulation prompted specific SMAD4 binding to all four SBEs. Luciferase reporter and SMAD4-knockdown experiments demonstrated that specific SMAD4 binding to the SBE located at -3790 bp to -3795 bp within the promoter region of CDH2 was necessary for TGF-β-stimulated transcription. Expression of N-cadherin on the surface of epithelial cells facilitates motility and invasion, and we demonstrated that knockdown of SMAD4 causes decreased N-cadherin expression, which results in diminished migration and invasion of human pancreatic ductal epithelial cells. Similar reduction of cell motility was produced after CDH2 knockdown. Together, these findings suggest that SMAD4 is critical for the TGF-β-driven upregulation of N-cadherin and the resultant invasive phenotype of human pancreatic ductal epithelial cells during EMT.

  10. Differential expression of aquaporin-3 and aquaporin-5 in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Direito, Inês; Paulino, Jorge; Vigia, Emanuel; Brito, Maria Alexandra; Soveral, Graça

    2017-06-01

    Aquaporin-5 (AQP5) and -3 (AQP3) are protein channels that showed to be up-regulated in a variety of tumors. Our goal was to investigate the expression pattern of AQP5 and AQP3 in pancreatic ductal adenocarcinomas (PDA) and correlate with cell proliferation, tumor stage and progression, and clinical significance. 35 PDA samples in different stages of differentiation and locations were analyzed by immunohistochemistry for expression of AQP5, AQP3 and several markers of cell proliferation and tumorigenesis. In PDA samples AQP5 was overexpressed in the apical membrane of intercalated and intralobular ductal cells while AQP3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. Simultaneous overexpression of EGFR, Ki-67, and CK7, with decreased E-cad and increased Vim that characterize epithelial mesenchymal transition, tumor formation and invasion, strongly suggest AQP3 and AQP5 involvement in cell proliferation and transformation. AQP3 overexpression is reinforced in late and more aggressive PDA stages whereas AQP5 is related with tumor differentiation, suggesting it may represent a novel marker for PDA aggressiveness and intestinal infiltration. These findings suggest AQP3 and AQP5 involvement in PDA development and the usefulness of AQP5 in early PDA diagnosis. © 2017 Wiley Periodicals, Inc.

  11. The neurotensin receptor-1 pathway contributes to human ductal breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Sandra Dupouy

    Full Text Available BACKGROUND: The neurotensin (NTS and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1, are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression.

  12. Staging of pancreatic ductal adenocarcinoma using dynamic MR imaging

    International Nuclear Information System (INIS)

    Murakami, Kouji; Nawano, Shigeru; Moriyama, Noriyuki; Sekiguchi, Ryuzou; Satake, Mituo; Iwata, Ryouko; Hayashi, Takayuki; Nemoto, Kazuhisa.

    1997-01-01

    Single breath-hold gradient echo images were obtained before and immediately after bolus intravenous administration of Gd-DTPA (dynamic MR imaging) in the study of the pancreas. Of 37 patients with pathologically proved pancreatic ductal adenocarcinoma, seventeen patients who underwent both dynamic MR imaging studies and curative surgery were included in this study. Correlations between histologic findings in the resected specimens and MR images were analyzed as to tumor extension and staging according to the General Rules for the Study of Pancreatic Cancer (4th Edition) published by the Japan Pancreas Society. In comparison with conventional MR images, dynamic MR imaging improved the detectability of pancreatic carcinoma and delineation of the vasculature by clarifying the margin of the tumor and the vessels. Nonenhanced T1-weighted imaging is the best sequence to estimate peripancreatic tumor extension, because the contrast between the tumor and peripancreatic fat deteriorates with the use of contrast material. There is a tendency to overestimate vascular invasion on MR images, the reason for which is considered to be the contractive nature of fibrotic change induced by pancreatic carcinoma. The diagnostic efficacy of lymph node metastasis remains insufficient on MR images because some cases show no enlargement of lymph nodes in spite of the existence of pathological metastasis. Our results suggest that dynamic MR imaging has the advantage of improving the conspicuity of the tumor and the vasculature. (author)

  13. Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study.

    Science.gov (United States)

    Williams, Lindsay A; Nichols, Hazel B; Hoadley, Katherine A; Tse, Chiu Kit; Geradts, Joseph; Bell, Mary Elizabeth; Perou, Charles M; Love, Michael I; Olshan, Andrew F; Troester, Melissa A

    2018-01-01

    Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+). In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.

  14. The diagnosis and management of pre-invasive breast disease: Promise of new technologies in understanding pre-invasive breast lesions

    International Nuclear Information System (INIS)

    Jeffrey, Stefanie S; Pollack, Jonathan R

    2003-01-01

    Array-based comparative genomic hybridization, RNA expression profiling, and proteomic analyses are new molecular technologies used to study breast cancer. Invasive breast cancers were originally evaluated because they provided ample quantities of DNA, RNA, and protein. The application of these technologies to pre-invasive breast lesions is discussed, including methods that facilitate their implementation. Data indicate that atypical ductal hyperplasia and ductal carcinoma in situ are precursor lesions molecularly similar to adjacent invasive breast cancer. It is expected that molecular technologies will identify breast tissue at risk for the development of unfavorable subtypes of invasive breast cancer and reveal strategies for targeted chemoprevention or eradication

  15. Getting the right balance in treatment of ductal carcinoma in situ (DCIS

    Directory of Open Access Journals (Sweden)

    Ian Stuart Fentiman

    2013-12-01

    Full Text Available As a result of mammographic detection, ductal carcinoma in situ (DCIS is an increasing problem in breast clinics. Both histopathology and molecular profiling can identify subtypes likely to progress to invasive disease, but there is no subgroup with a zero likelihood of subsequent invasion. In patients with low/intermediate grade DCIS, if breast irradiation is not being carried out after free margins have been achieved the patient should be aware of the risks of withholding and the benefits and morbidity of adjuvant radiotherapy. Either tamoxifen or an aromatase inhibitor may be of value in those with low/intermediate ER+ve disease if radiotherapy is being withheld. For those patients with extensive or multicentric DCIS, mastectomy is the appropriate treatment. This is best combined with sentinel node biopsy and all such cases should be offered immediate reconstruction.----------------------------Cite this article as:Fentiman IS. Getting the right balance in treatment of ductal carcinoma in situ (DCIS. Int J Cancer Ther Oncol 2013; 1(2:01029.DOI: http://dx.doi.org/10.14319/ijcto.0102.9 

  16. Fibroadenoma with "immature-like" type of usual ductal hyperplasia.

    Science.gov (United States)

    Bezić, Joško; Karaman, Ivana; Kunac, Nenad

    2016-01-01

    We herein report a case of the breast fibroadenoma with foci of so-called immature variant of the conventional ductal hyperplasia. This type of usual ductal hyperplasia is histologically characterised by encircling intraductal proliferation of large cells with pale to amphophilic cytoplasm and large nuclei which vary in shape and in staining quality of the chromatin. We showed here, using the cytokeratin immunohistochemistry, that the proliferating cells were not of immature but rather mature immunohistochemical phenotype. Because of the presented discordance between immature histology and mature immunohistological profile we suggest that this rare type of usual ductal hyperplasia should be called "immature-like".

  17. Unusual Metastatic Patterns of Invasive Lobular Carcinoma of the Breast

    OpenAIRE

    Sobinsky, Justin D.; Willson, Thomas D.; Podbielski, Francis J.; Connolly, Mark M.

    2013-01-01

    Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3?cm sigmoid aden...

  18. 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scan Findings for Ductal Carcinomas of Breast: Association of Standardized Uptake Value and Histological Findings

    Energy Technology Data Exchange (ETDEWEB)

    Bae, So Young; Lee, Eun Hye [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Park, Jung Mi [Dept. of Nuclear Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Kwak, Jeong Ja [Dept. of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2012-02-15

    To evaluate the factors associated with variations in 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) uptake in ductal carcinomas of the breast. We enrolled 216 ductal carcinoma cases that underwent 18F-FDG PET/CT. We evaluated the positivity and measured peak standardized uptake value (pSUV) of lesions that underwent 18F-FDG PET/CT. We analyzed the correlation between pSUV and invasiveness, lesion size, and the histologic factors of invasive ductal carcinoma (IDC). In the 18F-FDG PET/CT of ductal carcinomas, sensitivity was 90.2%, positive and negative predictive values were 99.5% and 25.0%, respectively. In ductal carcinoma in situ (DCIS) and IDC, the sensitivities were 68.8% and 92.0%, respectively. The mean pSUV of true positive (TP) DCIS and IDC were 2.6 and 5.1 (p < 0.05), respectively, whereas the false negative (FN) were 1.3 and 1.2 (p > 0.05), respectively, and that of false positive (FP) and true negative (TN) lesions were 2.2 and 0.9, respectively. The mean size of TP DCIS and IDC were 4.5 cm and 2.7 cm (p < 0.05), respectively, whereas the mean size of FN DCIS and IDC were 1.5 cm and 1.4 cm (p > 0.05), respectively, and that of FP and TN lesions were 1.8 cm and 1.2 cm respectively. Among the histological factors affecting IDC, mitosis showed the best correlation with pSUV (rho = 0.5). For 18F-FDG PET/CT of ductal carcinomas, the positive predictive value was 99.5% and the FN rate was 9.7%. False negative factors included DCIS and an IDC < 1.5 cm, whereas mitosis was the TP factor.

  19. Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study.

    Science.gov (United States)

    Catanzaro, Daniele; Shackney, Stanley E; Schaffer, Alejandro A; Schwartz, Russell

    2016-01-01

    Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints.

  20. Ductal carcinoma in situ: a proposal for a new classification

    NARCIS (Netherlands)

    Holland, R.; Peterse, J. L.; Millis, R. R.; Eusebi, V.; Faverly, D.; van de Vijver, M. J.; Zafrani, B.

    1994-01-01

    Details of a proposed new classification for ductal carcinoma in situ (DCIS) are presented. This is based, primarily, on cytonuclear differentiation and, secondarily, on architectural differentiation (cellular polarisation). Three categories are defined. First is poorly differentiated DCIS composed

  1. Molecular Markers of Metastasis in Ductal Mammary Carcinoma

    National Research Council Canada - National Science Library

    Achary, Patnala

    2002-01-01

    ...% of those patients, however, the disease spreads, and they are at risk of death. Our goal is to develop DNA markers that could be reliably used to identify the ductal mammary carcinomas that are prone to develop metastasis...

  2. Model organoids provide new research opportunities for ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Engle, Dannielle D; Tuveson, David A; Clevers, Hans

    We recently established organoid models from normal and neoplastic murine and human pancreas tissues. These organoids exhibit ductal- and disease stage-specific characteristics and, after orthotopic transplantation, recapitulate the full spectrum of tumor progression. Pancreatic organoid technology

  3. Denture hyperplasia with areas simulating oral inverted ductal papilloma.

    Science.gov (United States)

    Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

    2005-07-01

    Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

  4. Hyperspectral Imaging and K-Means Classification for Histologic Evaluation of Ductal Carcinoma In Situ

    Directory of Open Access Journals (Sweden)

    Yasser Khouj

    2018-02-01

    Full Text Available Hyperspectral imaging (HSI is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spectral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated that wavelengths near 550 nm showed the best differentiation between tissue types. This information was used to train image processing algorithms using supervised and unsupervised data. The K-means method was applied to the hyperspectral data cubes, and successfully detected spectral tissue differences with sensitivity of 85.45%, and specificity of 94.64% with true negative rate of 95.8%, and false positive rate of 4.2%. These results were verified by ground-truth marking of the tissue samples by a pathologist. In the hyperspectral image analysis, the image processing algorithm, K-means, shows the greatest potential for building a semi-automated system that could identify and sort between normal and ductal carcinoma in situ tissues.

  5. Hyperspectral Imaging and K-Means Classification for Histologic Evaluation of Ductal Carcinoma In Situ.

    Science.gov (United States)

    Khouj, Yasser; Dawson, Jeremy; Coad, James; Vona-Davis, Linda

    2018-01-01

    Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spectral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated that wavelengths near 550 nm showed the best differentiation between tissue types. This information was used to train image processing algorithms using supervised and unsupervised data. The K-means method was applied to the hyperspectral data cubes, and successfully detected spectral tissue differences with sensitivity of 85.45%, and specificity of 94.64% with true negative rate of 95.8%, and false positive rate of 4.2%. These results were verified by ground-truth marking of the tissue samples by a pathologist. In the hyperspectral image analysis, the image processing algorithm, K-means, shows the greatest potential for building a semi-automated system that could identify and sort between normal and ductal carcinoma in situ tissues.

  6. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

    NARCIS (Netherlands)

    Lips, Esther H.; Mukhtar, Rita A.; Yau, Christina; de Ronde, Jorma J.; Livasy, Chad; Carey, Lisa A.; Loo, Claudette E.; Vrancken-Peeters, Marie-Jeanne T. F. D.; Sonke, Gabe S.; Berry, Donald A.; van't Veer, Laura J.; Esserman, Laura J.; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E.

    2012-01-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene

  7. Radiologic Findings of Ductal Carcinoma in Situ Arising Within a Juvenile Fibroadenoma: Mammographic, Sonographic and Dynamic Contrast-Enhanced Breast MRI Features

    OpenAIRE

    Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Lee, Jeong Hyeon; Song, Sung Eun; Bae, Jeong Won

    2015-01-01

    Juvenile fibroadenoma is an uncommon histologic variant of fibroadenoma that frequently shows a remarkable and rapid growth. The development of a carcinoma within a fibroadenoma, either in situ or invasive, is a rare condition. We encountered a 36-year-old woman with a palpable mass in the right breast. The radiologic findings were indicative of a fibroadenoma in the breast. Sonographic guided biopsy using a 14G core needle revealed the presence of ductal carcinoma in situ (DCIS) within the j...

  8. Pain, sensory disturbances and psychological distress are common sequelae after treatment of ductal carcinoma in situ

    DEFF Research Database (Denmark)

    Mertz, Birgitte Goldschmidt; Duriaud, Helle Molter; Kroman, Niels

    2017-01-01

    Sequelae such as pain, sensory disturbances and psychological distress are well known after treatment for invasive breast cancer (IBC). Patients treated for ductal carcinoma in situ (DCIS) receive a similar treatment as low-risk IBC. The aim of this cross-sectional study was to describe prevalence......: 1.1–7.0, p = 0.02) and anxiety and depression (measured by HADStotal >15 OR of 3.1 (95% CI: 1.5–6.3, p = 0.003)) were significantly associated with moderate to severe pain. Approximately one-third of the patients reported sensory disturbances such as pins and needles (32%), numbness (37......%) and painful itch (30%) and 94 women (20%) reported anxiety ≥8, 26 (6%) depression and 51 (11%) reported distress. Conclusions: This cross-sectional study showed that women treated for DCIS suffered from pain, sensory disturbances and psychological impairment and had unmet rehabilitation needs. Further...

  9. Breast MRI of ductal carcinoma in situ. Is there MRI role?

    International Nuclear Information System (INIS)

    Francescutti, G.E.; Londero, V.; Berra, I.; Del Frate, C.; Zuiani, C.; Bazzocchi, M.

    2002-01-01

    Background. The purpose of this study is to report our personal experience of 22 cases of ductal carcinoma in situ (DCIS) studied with magnetic resonance imaging (MRI). Patients and methods. From September 1995 to December 2001, 22 women diagnosed with DCIS lesions underwent contrast enhanced MRI within 7 days after mammographic examination. Dynamic MRI was performed with a 1 T system, using a three dimensional fast low angle shot (FLASH) pulse sequence before and after contrast media administration. We evaluated the morphologic features of the enhancement, the enhancement rate and the signal time intensity curve. Pathology was obtained in all cases. Results. The results of histopatological examination included: 15 DCIS and 7 DCIS with associated microinvasive component or microfoci of invasive ductal carcinoma (IDC). On MRI, 21 of 22 (95%) DCIS lesions showed contrast enhancement. Fourteen out of 15 pure DCIS lesions demonstrated respectively a low (3), undeterminate (5), and strong (6) enhancement. Morphologically, the enhancing lesion was focal in 7, segmental in 4, and with linear branching in 3 cases. Wash out was found in 4 cases, plateau curve in 8 and Type I curve in 2 cases. Multifocality was present in 5 cases. All DCIS with associated microinvasion demonstrated contrast enhancement: 1/7 cases showed a low enhancement, 2/7 showed an indeterminate enhancement and 4/7 showed a strong enhancement. Morphologically, the enhancing lesion was focal in 3/9, segmental in 5 and with linear branching in 1 case. The wash out was demonstrated in 3/7 cases, plateau curve in 3 and Type 1 curve in 1 case. Multifocality was present in 3 cases. Conclusions. In conclusion, the sensitivity of MRI for DCIS detection is lower than that achieved for invasive breast cancer; however, contrast-enhanced MRI can depict foci of DCIS that are mammographically occult. The MRI technique is of complementary value for a better description of tumor size and detection of additional

  10. Ductal carcinoma in situ of the breast: can biomarkers improve current management?

    Science.gov (United States)

    Bartlett, John M S; Nofech-Moses, Sharon; Rakovitch, Eileen

    2014-01-01

    Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women. We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area. DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.

  11. Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Blair, Alex B; Zheng, Lei

    2017-06-01

    The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

  12. Mammary fibroadenoma: ductal pattern in pneumo-oncography

    International Nuclear Information System (INIS)

    Pinto Pabon, I.; Garcia Alvarez, A.; Castello Camerlinck, J.

    1988-01-01

    The authors present 25 cases affected by mammary fibroadenoma which underwent pneumo-oncography; in all instances they obtained a characteristic pattern of air distribution, the ductal pattern, which allows fibroadenoma to be reliably diagnosed. No carcinoma demonstrated this type of air pattern. 9 refs.; 3 figs

  13. The diagnosis and management of pre-invasive breast disease: Problems associated with management of pre-invasive lesions

    International Nuclear Information System (INIS)

    Purushotham, Anand D

    2003-01-01

    The treatment of ductal carcinoma in situ (DCIS) involves adequate surgical excision with adjuvant radiotherapy where appropriate. An inadequate excision margin and young age are independent risk factors for local recurrence. Routine surgery to axillary lymph nodes is not recommended in pure DCIS. In localised DCIS, adjuvant radiotherapy is recommended on the basis of tumour size, margin width and pathological subtypes. The role of adjuvant tamoxifen as systemic therapy is controversial. The treatment of atypical ductal/lobular hyperplasia and lobular carcinoma in situ involves surgical excision to exclude coexisting DCIS or invasive disease

  14. Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zou, Qiong; Yang, Zhulin; Li, Daiqiang; Liu, Ziru; Yuan, Yuan

    2016-12-01

    Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question. Immunohistochemistry of CLIC4 and Ihh was performed with EnVision ™ in 106 pancreatic ductal adenocarcinoma specimens, 35 paracancer samples (2 cm away from the tumour, when possible or available), 55 benign lesions and 13 normal tissue samples. CLIC4 and Ihh expression in pancreatic ductal adenocarcinoma were significantly higher than in paracancer tissue and benign lesions (CLIC4: P = 0.009 and Ihh: P Ihh: P = 0.0001 respectively). CLIC4 and Ihh expression was negative in normal pancreatic tissues. The expression of CLIC4 and Ihh was associated significantly with tumour grade, lymph node metastasis, tumour invasion and poor overall survival. Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

  15. Aberrant activation of NF-κB signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Barham, Whitney; Chen, Lianyi; Tikhomirov, Oleg; Onishko, Halina; Gleaves, Linda; Stricker, Thomas P.; Blackwell, Timothy S.; Yull, Fiona E.

    2015-01-01

    Approximately 1 in 5 women diagnosed with breast cancer are considered to have in situ disease, most often termed ductal carcinoma in situ (DCIS). Though recognized as a risk factor for the development of more invasive cancer, it remains unclear what factors contribute to DCIS development. It has been shown that inflammation contributes to the progression of a variety of tumor types, and nuclear factor kappa B (NF-κB) is recognized as a master-regulator of inflammatory signaling. However, the contributions of NF-κB signaling to tumor initiation are less well understood. Aberrant up-regulation of NF-κB activity, either systemically or locally within the breast, could occur due to a variety of commonly experienced stimuli such as acute infection, obesity, or psychological stress. In this study, we seek to determine if activation of NF-κB in mammary epithelium could play a role in the formation of hyperplastic ductal lesions. Our studies utilize a doxycycline-inducible transgenic mouse model in which constitutively active IKKβ is expressed specifically in mammary epithelium. All previously published models of NF-κB modulation in the virgin mammary gland have been constitutive models, with transgene or knock-out present throughout the life and development of the animal. For the first time, we will induce activation at later time points after normal ducts have formed, thus being able to determine if NF-κB activation can promote pre-malignant changes in previously normal mammary epithelium. We found that even a short pulse of NF-κB activation could induce profound remodeling of mammary ductal structures. Short-term activation created hyperproliferative, enlarged ducts with filled lumens. Increased expression of inflammatory markers was concurrent with the down-regulation of hormone receptors and markers of epithelial differentiation. Furthermore, the oncoprotein mucin 1, known to be up-regulated in human and mouse DCIS, was over-expressed and mislocalized in the

  16. Sentinel lymph node biopsy in patients with a needle core biopsy diagnosis of ductal carcinoma in situ: is it justified?

    LENUS (Irish Health Repository)

    Doyle, B

    2012-02-01

    BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly with the introduction of population-based mammographic screening. DCIS is usually diagnosed non-operatively. Although sentinel lymph node biopsy (SNB) has become the standard of care for patients with invasive breast carcinoma, its use in patients with DCIS is controversial. AIM: To examine the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. METHODS: A retrospective analysis was performed of 145 patients with an NCB diagnosis of DCIS who had SNB performed at the time of primary surgery. The study focused on rates of SNB positivity and underestimation of invasive carcinoma by NCB, and sought to identify factors that might predict the presence of invasive carcinoma in the excision specimen. RESULTS: 7\\/145 patients (4.8%) had a positive sentinel lymph node, four macrometastases and three micrometastases. 6\\/7 patients had invasive carcinoma in the final excision specimen. 55\\/145 patients (37.9%) with an NCB diagnosis of DCIS had invasive carcinoma in the excision specimen. The median invasive tumour size was 6 mm. A radiological mass and areas of invasion <1 mm, amounting to "at least microinvasion" on NCB were predictive of invasive carcinoma in the excision specimen. CONCLUSIONS: SNB positivity in pure DCIS is rare. In view of the high rate of underestimation of invasive carcinoma in patients with an NCB diagnosis of DCIS in this study, SNB appears justified in this group of patients.

  17. Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

    Science.gov (United States)

    Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

    2014-10-01

    Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.

    Science.gov (United States)

    Li, Jing; Luo, Miaosha; Wang, Yan; Shang, Boxin; Dong, Lei

    2016-09-01

    The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.

  19. Long term clinical follow-up of atypical ductal hyperplasia and lobular carcinoma in situ in breast core needle biopsies.

    Science.gov (United States)

    Renshaw, Andrew A; Gould, Edwin W

    2016-01-01

    Atypical ductal hyperplasia (ADH) and lobular carcinoma in situ (LCIS) may be associated with a relatively high incidence of invasive carcinoma and ductal carcinoma in situ (DCIS) on immediate excision when found on core needle biopsy of the breast. However, the long term significance of ADH and LCIS in a breast core needle biopsy is not as well characterised. We reviewed the results of all breast core needle biopsies with a diagnosis of ADH or LCIS and immediate excision from the years 2000-2004, and correlated the results with long term clinical follow-up. Of 175 biopsies with ADH, 53 (30.3%) had carcinoma (8 invasive, and 45 DCIS) at the time of immediate re-excision. Of 69 biopsies with LCIS, three (4.3%) had carcinoma (2 invasive, and 1 DCIS) at the time of immediate re-excision. A total of 14 (11.5%) patients with ADH and benign re-excisions developed invasive carcinoma (12) or DCIS (2) on follow-up. A total of 17 (25.8%) patients with LCIS and benign re-excisions developed invasive carcinoma (13) or DCIS (4) on follow-up. The risk of invasive carcinoma or DCIS on immediate re-excision was significantly higher for women with ADH than LCIS (pfibrocystic changes (FCC) on core needle biopsy, the risk of developing invasive carcinoma or DCIS was significantly higher for women with ADH and benign initial re-excisions (95% CI 1.092-7.297, p=0.03), and women with LCIS and benign re-excisions (95% CI 3.028-18.657, p<0.001). Overall, 67/175 (38.3%) women with ADH and 20/69 (29.0%) women with LCIS on core needle biopsy either had carcinoma at the time of the biopsy or later developed carcinoma. Significantly more women with LCIS developed invasive carcinoma or DCIS than women with ADH on long term follow-up. The relative risk for ADH and LCIS on core biopsy with a negative excision compared with FCC was similar to that reported in the literature (ADH 1-7×, LCIS 3-19×). Copyright © 2015 The Royal College of Pathologists of Australasia. Published by Elsevier B.V. All

  20. Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance

    Directory of Open Access Journals (Sweden)

    Sha JJ

    2013-10-01

    Full Text Available Jianjun Sha,1,2 Juanjie Bo,1 Jiahua Pan,1 Lianhua Zhang,1 Hanqing Xuan,1 Wei Chen,1 Dong Li,1 Zhaoliang Wang,1 Dongming Liu,1 Yiran Huang1,2 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 2School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China Introduction: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. Methods: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI, bone scan, cystoscopy, and computed tomography (CT scan. The level of prostate-specific antigen (PSA before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. Results: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57–88. Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was

  1. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis.

    Science.gov (United States)

    Besmer, Dahlia M; Curry, Jennifer M; Roy, Lopamudra D; Tinder, Teresa L; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y; Gendler, Sandra J; Mukherjee, Pinku

    2011-07-01

    MUC1 is overexpressed and aberrantly glycosylated in more than 60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In this study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared with both KC and KCM. Cell lines derived from KCKO tumors have significantly less tumorigenic capacity compared with cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared with mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor, platelet-derived growth factor, or matrix metalloproteinase 9. Further, significantly less KCKO cells entered the G(2)-M phase of the cell cycle compared with the KCM cells. Proteomics and Western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of mitogen-activated protein kinase (MAPK), as well as a significant decrease in nestin and tubulin-α2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. ©2011 AACR

  2. Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.

    LENUS (Irish Health Repository)

    Pradeep, C-R

    2012-02-16

    A large fraction of ductal carcinoma in situ (DCIS), a non-invasive precursor lesion of invasive breast cancer, overexpresses the HER2\\/neu oncogene. The ducts of DCIS are abnormally filled with cells that evade apoptosis, but the underlying mechanisms remain incompletely understood. We overexpressed HER2 in mammary epithelial cells and observed growth factor-independent proliferation. When grown in extracellular matrix as three-dimensional spheroids, control cells developed a hollow lumen, but HER2-overexpressing cells populated the lumen by evading apoptosis. We demonstrate that HER2 overexpression in this cellular model of DCIS drives transcriptional upregulation of multiple components of the Notch survival pathway. Importantly, luminal filling required upregulation of a signaling pathway comprising Notch3, its cleaved intracellular domain and the transcriptional regulator HES1, resulting in elevated levels of c-MYC and cyclin D1. In line with HER2-Notch3 collaboration, drugs intercepting either arm reverted the DCIS-like phenotype. In addition, we report upregulation of Notch3 in hyperplastic lesions of HER2 transgenic animals, as well as an association between HER2 levels and expression levels of components of the Notch pathway in tumor specimens of breast cancer patients. Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS.

  3. Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

    Science.gov (United States)

    Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

    2018-04-02

    Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. The adaptor protein CrkII regulates IGF-1-induced biological behaviors of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Liu, Rui; Wang, Qing; Xu, Guangying; Li, Kexin; Zhou, Lingli; Xu, Baofeng

    2016-01-01

    Recently, the adaptor protein CrkII has been proved to function in initiating signals for proliferation and invasion in some malignancies. However, the specific mechanisms underlying insulin-like growth factor 1 (IGF-1)-CrkII signaling-induced proliferation of pancreatic ductal adenocarcinoma (PDAC) were not unraveled. In this work, PDAC tissues and cell lines were subjected to in vitro and in vivo assays. Our findings showed that CrkII was abundantly expressed in PDAC tissues and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When cells were subjected to si-CrkII, si-CrkII inhibited IGF-1-mediated PDAC cell growth. In vitro, we demonstrated the upregulation of CrkII, p-Erk1/2, and p-Akt occurring in IGF-1-treated PDAC cells. Conversely, si-CrkII affected upregulation of CrkII, p-Erk1/2, and p-Akt. In addition, cell cycle and in vivo assay identified that knockdown of CrkII inhibited the entry of G1 into S phase and the increase of PDAC tumor weight. In conclusion, CrkII mediates IGF-1 signaling and further balanced PDAC biological behaviors via Erk1/2 and Akt pathway, which indicates that CrkII gene and protein may act as an effective target for the treatment of PDAC.

  5. Improving classification with forced labeling of other related classes: application to prediction of upstaged ductal carcinoma in situ using mammographic features

    Science.gov (United States)

    Hou, Rui; Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2018-02-01

    Predicting whether ductal carcinoma in situ (DCIS) identified at core biopsy contains occult invasive disease is an import task since these "upstaged" cases will affect further treatment planning. Therefore, a prediction model that better classifies pure DCIS and upstaged DCIS can help avoid overtreatment and overdiagnosis. In this work, we propose to improve this classification performance with the aid of two other related classes: Atypical Ductal Hyperplasia (ADH) and Invasive Ductal Carcinoma (IDC). Our data set contains mammograms for 230 cases. Specifically, 66 of them are ADH cases; 99 of them are biopsy-proven DCIS cases, of whom 25 were found to contain invasive disease at the time of definitive surgery. The remaining 65 cases were diagnosed with IDC at core biopsy. Our hypothesis is that knowledge can be transferred from training with the easier and more readily available cases of benign but suspicious ADH versus IDC that is already apparent at initial biopsy. Thus, embedding both ADH and IDC cases to the classifier will improve the performance of distinguishing upstaged DCIS from pure DCIS. We extracted 113 mammographic features based on a radiologist's annotation of clusters.Our method then added both ADH and IDC cases during training, where ADH were "force labeled" or treated by the classifier as pure DCIS (negative) cases, and IDC were labeled as upstaged DCIS (positive) cases. A logistic regression classifier was built based on the designed training dataset to perform a prediction of whether biopsy-proven DCIS cases contain invasive cancer. The performance was assessed by repeated 5-fold CrossValidation and Receiver Operating Characteristic(ROC) curve analysis. While prediction performance with only training on DCIS dataset had an average AUC of 0.607(%95CI, 0.479-0.721). By adding both ADH and IDC cases for training, we improved the performance to 0.691(95%CI, 0.581-0.801).

  6. Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion

    International Nuclear Information System (INIS)

    Okumura, Yasuhiro; Iwase, Hirotaka; Yamamoto, Yutaka; Zhang, Zhenhuan; Toyama, Tatsuya; Kawasoe, Teru; Ibusuki, Mutsuko; Honda, Yumi; Iyama, Ken-ichi; Yamashita, Hiroko

    2008-01-01

    Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness. In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion. Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance

  7. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C.; Quan, Liao; Yupei, Zhao; Friess, Helmut; Erkan, Mert; Kleeff, Joerg

    2010-01-01

    Research highlights: → The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. → Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. → BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. → BHLHB2 is an independent prognostic factor in multivariable cox analysis with a hazard ratio of 2:4. -- Abstract: Aims: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer were investigated. Methods: Expression analyses were carried out in tissues of the normal pancreas (n = 10) and pancreatic ductal adenocarcinoma (n = 77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. Results: BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 ± 1.353 to 38.70 ± 5.262 nM (p < 0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and pancreatic cancer cells. Patients with

  8. Microinvasive ductal carcinoma in situ: Clinical presentation, imaging features, pathologic findings, and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, Cristina C. [Department of Radiology, New York University School of Medicine (United States); Mercado, Cecilia L. [Department of Radiology, New York University School of Medicine (United States)], E-mail: Cecilia.mercado@nyumc.org; Cangiarella, Joan F. [Department of Pathology, New York University School of Medicine (United States); Moy, Linda; Toth, Hildegard K. [Department of Radiology, New York University School of Medicine (United States); Guth, Amber A. [Department of Surgery, New York University School of Medicine (United States)

    2010-01-15

    Objective: The purpose of our study was to describe the clinical features, imaging characteristics, pathologic findings and outcome of microinvasive ductal carcinoma in situ (DCISM). Materials and methods: The records of 21 women diagnosed with microinvasive ductal carcinoma in situ (DCISM) from November 1993 to September 2006 were retrospectively reviewed. The clinical presentation, imaging and histopathologic features, and clinical follow-up were reviewed. Results: The 21 lesions all occurred in women with a mean age of 56 years (range, 27-79 years). Clinical findings were present in ten (48%): 10 with palpable masses, four with associated nipple discharge. Mean lesion size was 21 mm (range, 9-65 mm). The lesion size in 62% was 15 mm or smaller. Mammographic findings were calcifications only in nine (43%) and an associated or other finding in nine (43%) [mass (n = 7), asymmetry (n = 1), architectural distortion (n = 1)]. Three lesions were mammographically occult. Sonographic findings available in 11 lesions showed a solid hypoechoic mass in 10 cases (eight irregular in shape, one round, one oval). One lesion was not seen on sonography. On histopathologic examination, all lesions were diagnosed as DCISM, with a focus of invasive carcinoma less than or equal to 1 mm in diameter within an area of DCIS. Sixteen (76%) lesions were high nuclear grade, four (19%) were intermediate and one was low grade (5%). Sixteen (76%) had the presence of necrosis. Positivity for ER and PR was noted in 75% and 38%. Nodal metastasis was present in one case with axillary lymph node dissection. Mean follow-up time for 16 women was 36 months without evidence of local or systemic recurrence. One patient developed a second primary in the contralateral breast 3 years later. Conclusion: The clinical presentation and radiologic appearance of a mass are commonly encountered in DCISM lesions (48% and 57%, respectively), irrespective of lesion size, mimicking findings seen in invasive carcinoma

  9. Microinvasive ductal carcinoma in situ: Clinical presentation, imaging features, pathologic findings, and outcome

    International Nuclear Information System (INIS)

    Vieira, Cristina C.; Mercado, Cecilia L.; Cangiarella, Joan F.; Moy, Linda; Toth, Hildegard K.; Guth, Amber A.

    2010-01-01

    Objective: The purpose of our study was to describe the clinical features, imaging characteristics, pathologic findings and outcome of microinvasive ductal carcinoma in situ (DCISM). Materials and methods: The records of 21 women diagnosed with microinvasive ductal carcinoma in situ (DCISM) from November 1993 to September 2006 were retrospectively reviewed. The clinical presentation, imaging and histopathologic features, and clinical follow-up were reviewed. Results: The 21 lesions all occurred in women with a mean age of 56 years (range, 27-79 years). Clinical findings were present in ten (48%): 10 with palpable masses, four with associated nipple discharge. Mean lesion size was 21 mm (range, 9-65 mm). The lesion size in 62% was 15 mm or smaller. Mammographic findings were calcifications only in nine (43%) and an associated or other finding in nine (43%) [mass (n = 7), asymmetry (n = 1), architectural distortion (n = 1)]. Three lesions were mammographically occult. Sonographic findings available in 11 lesions showed a solid hypoechoic mass in 10 cases (eight irregular in shape, one round, one oval). One lesion was not seen on sonography. On histopathologic examination, all lesions were diagnosed as DCISM, with a focus of invasive carcinoma less than or equal to 1 mm in diameter within an area of DCIS. Sixteen (76%) lesions were high nuclear grade, four (19%) were intermediate and one was low grade (5%). Sixteen (76%) had the presence of necrosis. Positivity for ER and PR was noted in 75% and 38%. Nodal metastasis was present in one case with axillary lymph node dissection. Mean follow-up time for 16 women was 36 months without evidence of local or systemic recurrence. One patient developed a second primary in the contralateral breast 3 years later. Conclusion: The clinical presentation and radiologic appearance of a mass are commonly encountered in DCISM lesions (48% and 57%, respectively), irrespective of lesion size, mimicking findings seen in invasive carcinoma

  10. Patients with Invasive Lobular Breast Cancer Are Less Likely to Undergo Breast-Conserving Surgery: A Population Based Study in The Netherlands

    NARCIS (Netherlands)

    Truin, W.; Roumen, R.M.; Siesling, Sabine; van der Heiden-van der Loo, M.; Duijm, E.M.; Tjan-Heijnen, V.C.G.; Voogd, A.C.

    2015-01-01

    Purpose The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). Methods Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the

  11. Invasive Candidiasis

    Science.gov (United States)

    ... Waterborne, and Environmental Diseases Mycotic Diseases Branch Invasive Candidiasis Recommend on Facebook Tweet Share Compartir Global Emergence ... antifungal drugs. Learn more about C. auris Invasive candidiasis is an infection caused by a yeast (a ...

  12. TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

    Science.gov (United States)

    Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

    2009-03-01

    Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

  13. Radiologic Findings of Ductal Carcinoma in Situ Arising Within a Juvenile Fibroadenoma: Mammographic, Sonographic and Dynamic Contrast-Enhanced Breast MRI Features

    International Nuclear Information System (INIS)

    Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Lee, Jeong Hyeon; Song, Sung Eun; Bae, Jeong Won

    2015-01-01

    Juvenile fibroadenoma is an uncommon histologic variant of fibroadenoma that frequently shows a remarkable and rapid growth. The development of a carcinoma within a fibroadenoma, either in situ or invasive, is a rare condition. We encountered a 36-year-old woman with a palpable mass in the right breast. The radiologic findings were indicative of a fibroadenoma in the breast. Sonographic guided biopsy using a 14G core needle revealed the presence of ductal carcinoma in situ (DCIS) within the juvenile fibroadenoma. Focal excision was performed and the patient underwent radiation therapy in the right breast after surgery

  14. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

    Science.gov (United States)

    Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

    2009-09-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

  15. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    Science.gov (United States)

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-06-02

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. 2016 BMJ Publishing Group Ltd.

  16. Current trials to reduce surgical intervention in ductal carcinoma in situ of the breast: Critical review.

    Science.gov (United States)

    Toss, M; Miligy, I; Thompson, A M; Khout, H; Green, A R; Ellis, I O; Rakha, E A

    2017-10-01

    The high proportion of ductal carcinoma in situ (DCIS) presented in mammographic screening and the relatively low risk of progression to invasive disease have raised questions related to overtreatment. Following a review of current DCIS management protocols a more conservative approach has been suggested. Clinical trials have been introduced to evaluate the option of avoiding surgical intervention in a proportion of patients with DCIS defined as "low-risk" using certain clinicopathological criteria. These trials can potentially provide evidence-based models of active surveillance (with or without endocrine therapy) as a future management approach. Despite the undisputable fact of our need to address the obvious overtreatment of screen-detected DCIS, some important questions need to be considered regarding these trials including the eligibility criteria and definition of risk, the proportion of patient eligible for inclusion, and the length of time required for proper analysis of the trials' outcome in view of the long-term natural history of DCIS progression particularly the low-risk group. These factors can potentially affect the practicality and future impact of such trials. This review provides critical analysis of current DCIS management trials and highlights critical issues related to their practicality and the expected outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Is Radiation Indicated in Patients With Ductal Carcinoma In Situ and Close or Positive Mastectomy Margins?

    International Nuclear Information System (INIS)

    Chan, Linda W.; Rabban, Joseph; Hwang, E. Shelley; Bevan, Alison; Alvarado, Michael; Ewing, Cheryl; Esserman, Laura; Fowble, Barbara

    2011-01-01

    Purpose: Resection margin status is one of the most significant factors for local recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery with or without radiation. However, its impact on chest wall recurrence in patients treated with mastectomy is unknown. The purpose of this study was to determine chest wall recurrence rates in women with DCIS and close ( 5 cm or diffuse disease. Median width of the close final margin was 2 mm. Nineteen patients had margins of <1 mm. One of these 59 patients experienced a chest wall recurrence with regional adenopathy, followed by distant metastases 2 years following skin-sparing mastectomy. The DCIS was high-grade, 4 cm, with a 5-mm deep margin. A second patient developed an invasive cancer in the chest wall 20 years after her mastectomy for DCIS. This cancer was considered a new primary site arising in residual breast tissue. Conclusions: The risk of chest wall recurrence in this series of patients is 1.7% for all patients and 3.3% for high-grade DCIS. One out of 20 (5%) patients undergoing skin sparing or total skin-sparing mastectomy experienced a chest wall recurrence. This risk of a chest wall recurrence appears sufficiently low not to warrant a recommendation for postmastectomy radiation therapy for patients with margins of <5 mm. There were too few patients with positive margins to draw any firm conclusions.

  18. Contrast enhanced MRI findings of ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Kang, Bong Joo; Cha, Eun Suk; Kim, Hyeon Sook; Suh, Young Jin; Choi, Hyun Joo

    2006-01-01

    The purpose of this study is to describe characteristic contrast enhanced MR mammographic findings of ductal carcinoma in situ (DCIS) and also DCIS with microinvasion. From January 2000 to July 2005, 32 women with 33 lesions affected by DCIS or DCIS with microinvasion underwent contrast enhanced MRI, and they were then retrospectively evaluated. All the patients had previously undergone mammography and ultrasonography. All the findings of mammography, ultrasonography (US), and MRI were analyzed by using an ACR BI-RADS lexicon. All 33 cases were enhanced on the enhanced MR images. A smooth margined homogeneous enhanced mass was seen in the two (2/33) cases, and nonmass enhancement was seen in 31 (31/33) cases. Among the non-mass enhancement, focal enhancement (7/31), ductal enhancement (5/31), segmental enhancement (9/31), and regional enhancement (10/31) were observed. On the kinetic study, a wash-out pattern (10/33), a plateau pattern (20/33), and a persistent pattern (3/33) were demonstrated. No significant differences were noted between the pure and microinvasive DCIS. There is no significant difference between pure and microinvasive DCIS. However, contrast enhanced MR images can demonstrate occult foci, multifocal lesion and the tumor extent of DCIS on mammogram or ultrasonogram

  19. Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Biankin, Andrew V; Kench, James G; Dijkman, Floriaan P; Biankin, Sandra A; Henshall, Susan M

    2003-02-01

    Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.

  20. Expression analysis of carbohydrate antigens in ductal carcinoma in situ of the breast by lectin histochemistry

    Directory of Open Access Journals (Sweden)

    Kieber-Emmons Thomas

    2008-05-01

    Full Text Available Abstract Background The number of breast cancer patients diagnosed with ductal carcinoma in situ (DCIS continues to grow. Laboratory and clinical data indicate that DCIS can progress to invasive disease. Carbohydrate-mediated cell-cell adhesion and tumor-stroma interaction play crucial roles in tumorigenesis and tumor aggressive behavior. Breast carcinogenesis may reflect quantitative as well as qualitative changes in oligosaccharide expression, which may provide a useful tool for early detection of breast cancer. Because tumor-associated carbohydrate antigens (TACA are implicated in tumor invasion and metastasis, the purpose of this study was to assess the expression of selected TACA by lectin histochemistry on DCIS specimens from the archival breast cancer tissue array bank of the University of Arkansas for Medical Sciences. Methods For detection of TACA expression, specimens were stained with Griffonia simplicifolia lectin-I (GS-I and Vicia vilosa agglutinin (VVA. We studied associations of lectin reactivity with established prognostic factors, such as tumor size, tumor nuclear grade, and expression of Her-2/neu, p53 mutant and estrogen and progesterone receptors. Results We observed that both lectins showed significant associations with nuclear grade of DCIS. DCIS specimens with nuclear grades II and III showed significantly more intense reactivity than DCIS cases with nuclear grade I to GS-1 (Mean-score chi-square = 17.60, DF = 2; P = 0.0002 and VVA (Mean-score chi-square = 15.72, DF = 2; P = 0.0004. Conclusion The results suggest that the expression of VVA- and GS-I-reactive carbohydrate antigens may contribute to forming higher grade DCIS and increase the recurrence risk.

  1. Expression analysis of carbohydrate antigens in ductal carcinoma in situ of the breast by lectin histochemistry

    International Nuclear Information System (INIS)

    Korourian, Soheila; Siegel, Eric; Kieber-Emmons, Thomas; Monzavi-Karbassi, Behjatolah

    2008-01-01

    The number of breast cancer patients diagnosed with ductal carcinoma in situ (DCIS) continues to grow. Laboratory and clinical data indicate that DCIS can progress to invasive disease. Carbohydrate-mediated cell-cell adhesion and tumor-stroma interaction play crucial roles in tumorigenesis and tumor aggressive behavior. Breast carcinogenesis may reflect quantitative as well as qualitative changes in oligosaccharide expression, which may provide a useful tool for early detection of breast cancer. Because tumor-associated carbohydrate antigens (TACA) are implicated in tumor invasion and metastasis, the purpose of this study was to assess the expression of selected TACA by lectin histochemistry on DCIS specimens from the archival breast cancer tissue array bank of the University of Arkansas for Medical Sciences. For detection of TACA expression, specimens were stained with Griffonia simplicifolia lectin-I (GS-I) and Vicia vilosa agglutinin (VVA). We studied associations of lectin reactivity with established prognostic factors, such as tumor size, tumor nuclear grade, and expression of Her-2/neu, p53 mutant and estrogen and progesterone receptors. We observed that both lectins showed significant associations with nuclear grade of DCIS. DCIS specimens with nuclear grades II and III showed significantly more intense reactivity than DCIS cases with nuclear grade I to GS-1 (Mean-score chi-square = 17.60, DF = 2; P = 0.0002) and VVA (Mean-score chi-square = 15.72, DF = 2; P = 0.0004). The results suggest that the expression of VVA- and GS-I-reactive carbohydrate antigens may contribute to forming higher grade DCIS and increase the recurrence risk

  2. SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression.

    Directory of Open Access Journals (Sweden)

    Chuntao Gao

    Full Text Available Stem cell factor (SCF and hypoxia-inducible factor-1α (HIF-1α both have important functions in pancreatic ductal adenocarcinoma (PDAC. This study aims to analyze the expression and clinicopathological significance of SCF and HIF-1α in PDAC specimens and explore the molecular mechanism at PDAC cells in vitro and in vivo. We showed that the expression of SCF was significantly correlated with HIF-1α expression via Western blot, PCR, chromatin immunoprecipitation (ChIP assay, and luciferase assay analysis. The SCF level was also correlated with lymph node metastasis and the pathological tumor node metastasis (pTNM stage in PDAC samples. The SCF higher-expression group had significantly lower survival rates than the SCF lower-expression group (p<0.05. Hypoxia up-regulated the expression of SCF through the hypoxia-inducible factor (HIF-1α in PDAC cells at the protein and RNA levels. When HIF-1α was knocked down by RNA interference, the SCF level decreased significantly. Additionally, ChIP and luciferase results demonstrated that HIF-1α can directly bind to the hypoxia response element (HRE region of the SCF promoter and activate the SCF transcription under hypoxia. The results of colony formation, cell scratch, and transwell migration assay showed that SCF promoted the proliferation and invasion of PANC-1 cells under hypoxia. Furthermore, the down-regulated ability of cell proliferation and invasion following HIF-1α knockdown was rescued by adding exogenous SCF under hypoxia in vitro. Finally, when the HIF-1α expression was inhibited by digoxin, the tumor volume and the SCF level decreased, thereby proving the relationship between HIF-1α and SCF in vivo. In conclusion, SCF is an important factor for the growth of PDAC. In our experiments, we proved that SCF, a downstream gene of HIF-1α, can promote the development of PDAC under hypoxia. Thus, SCF might be a potential therapeutic target for PDAC.

  3. Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Kapo Saukkonen

    Full Text Available Podocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC. The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associations of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher's exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier analysis and the Cox proportional hazard model.The polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0% specimens and the monoclonal antibody was highly expressed in 36 (21.8% cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045 and perineural invasion (p=0.005, and high expression by the mono-clonal antibody with poor differentiation (p=0.033. High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR = 1.62; 95% confidence interval (CI 1.12-2.33; p=0.01 and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001. The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%, and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001.We found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value.

  4. Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.

    Science.gov (United States)

    Detremerie, Celine; Timmermans, Frank; De Pauw, Michel; Gheeraert, Peter; Hemelsoet, Dimitri; Toeback, Jonas; Bové, Thierry; Vandecasteele, Els

    2017-08-01

    We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.

  5. ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity

    OpenAIRE

    Eom, Minseob; Lkhagvadorj, Sayamaa; Oh, Sung Soo; Han, Airi; Park, Kwang Hwa

    2013-01-01

    Purpose ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression pa...

  6. Tumor Microenvironment and Progression to Invasion after a Diagnosis of Ductal Carcinoma In Situ

    Science.gov (United States)

    2013-11-01

    Distribution Unlimited The views , opinions and/or findings contained in this report are those...study of cases diagnosed between 1995 and 2006, this gap had narrowed to 3.1 versus 1.3 %, respectively. These results suggest that in community practice...Ruhl J, Tatalovich Z, Cho H et al (2012) SEER cancer statistics review, 1975–2009. National Cancer Institute, Bethesda, MD. http://seer.cancer.gov/ csr

  7. Nerve Invasion by Epithelial Cells in Benign Breast Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jan Chan

    2009-03-01

    Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

  8. Variations in the management of the axilla in screen-detected ductal carcinoma in situ: evidence from the UK NHS breast screening programme audit of screen detected DCIS.

    Science.gov (United States)

    Nicholson, S; Hanby, A; Clements, K; Kearins, O; Lawrence, G; Dodwell, D; Bishop, H; Thompson, A

    2015-01-01

    The diagnosis and surgical management of screen-detected Ductal Carcinoma In Situ (DCIS) remains controversial including a range of axillary approaches and consequent morbidity. This study examined the management of the axilla in all patients with DCIS presenting through the United Kingdom National Health Service Breast Screening Programme (UK NHS BSP). Retrospective analysis of the UK NHS BSP identified 26,696 women initially diagnosed with DCIS over the 8 years 1 April 2003-31 March 2011. The final breast pathology of these women was upgraded to invasive ductal cancer in 5564 (20.8%) women or micro-invasive cancer in 1031 (3.9%) women. At first operation, 5290 (26.3%) of the 20,094 women who had a final post-operative diagnosis of DCIS only underwent axillary surgery (72.4% at the time of mastectomy, 23.8% breast conservation surgery, 3.8% axillary surgery alone). Performance of axillary surgery reflected increasing tumour size, micro-invasion or increasing nuclear grade for the final diagnosis of DCIS. More extensive nodal surgery was performed in those undergoing mastectomy; 10.8% of women had more than 8 nodes removed. Overall, 12.0% of women with invasive cancer, 1.7% with micro-invasion, and 0.2% with DCIS alone, were ultimately node positive. Improved pre-operative sampling of DCIS, axillary assessment by ultrasound with needle biopsy for suspected metastases, risk stratification for sentinel node biopsy (for high grade or extensive DCIS) and avoiding axillary clearance for a pre-operative diagnosis of DCIS alone should reduce unnecessary axillary surgery. Standards using such criteria for axillary surgery in screen-detected DCIS should be integrated into the NHS BSP. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  9. Ductal adenocarcinoma and unusual differential diagnosis; Duktales Adenokarzinom und ungewoehnliche Differenzialdiagnosen

    Energy Technology Data Exchange (ETDEWEB)

    Haage, P.; Schwartz, C.A.; Scharwaechter, C. [Universitaet Witten/Herdecke, Zentrum fuer Radiologie HELIOS Universitaetsklinikum Wuppertal, Wuppertal (Germany)

    2016-04-15

    Ductal pancreatic adenocarcinoma is by far the most common solid tumor of the pancreas. It has a very poor prognosis, especially in the more advanced stages which are no longer locally confined. Due to mostly unspecific symptoms, imaging is key in the diagnostic process. Because of the widespread use of imaging techniques, incidental findings are to a greater extent discovered in the pancreas, which subsequently entail further work-up. Ductal pancreatic adenocarcinoma can be mimicked by a large number of different lesions, such as anatomical variants, peripancreatic structures and tumors, rarer primary solid pancreatic tumors, cystic tumors, metastases or different variants of pancreatitis. Additionally, a number of precursor lesions can be differentiated. The correct classification is thus important as an early diagnosis of ductal pancreatic adenocarcinoma is relevant for the prognosis and because the possibly avoidable treatment is very invasive. All major imaging techniques are principally suitable for pancreatic imaging. In addition to sonography of the abdomen, usually the baseline diagnostic tool, computed tomography (CT) with its superior spatial resolution, magnetic resonance imaging (MRI) with its good soft tissue differentiation capabilities, possibly in combination with MR cholangiopancreatography (MRCP), endosonography with its extraordinary spatial resolution, conceivably with additional endoscopic retrograde CP or the option of direct biopsy and finally positron emission tomography CT (PET-CT) as a molecular imaging tool are all particularly useful modalities. The various techniques all have its advantages and disadvantages; depending on the individual situation they may need to be combined. (orig.) [German] Das duktale Adenokarzinom ist der weitaus haeufigste solide Tumor des Pankreas. Die Prognose ist sehr schlecht, insbesondere bei fortgeschrittenen, nicht mehr lokal begrenzten Tumoren. Bei meist unspezifischen geringen Beschwerden kommt der

  10. Atypical ductal hyperplasia of the breast: radiologic and histopathologic correlation

    International Nuclear Information System (INIS)

    Lee, Ji Young; Kim, Jung Hyck; Oh, Yu Whan; Cho, Kyu Ran; Choi, Eun Jeong; Je, Bo Kyoung; Lee, Ji Hae; Seo, Bo Kyoung

    2003-01-01

    To evaluate the clinical and radiologic findings of atypical ductal hyperplasia (ADH) using mammography and ultrasonography, and to correlate the radiologic and histopathologic findings. Sixty-four pathologically proven lesions in 64 patients who were examined between March 2000 and March 2003 were the subject of this study. Mammography was performed in all 64 cases, and ultrasonography in 30. Two radiologists retrospectively evaluated the radiologic findings, classifying them as one of four types: mass, microcalcification, other finding, and no detected lesion. At mammography, masses were classified according to their shape, margin, and density and microcalcifications according to their shape and distribution. At ultrasonography, masses were evaluated in terms of their shape, margin, internal and posterior echotexture, ductal extension, and parallelism to skin. Geographic correlation between the radiologic and histopathologic findings was classified as direct, near direct, or remote correlation. Mammography demonstrated 37 cases of microcalcification (57.8%), 14 in which masses were present (21.9%), two in which there were other findings (3.1%), and 11 in which lesions were not detected (17.2%). The 'other finding' was ductectasia. Microcalcifications were round in 19 cases, pleomorphic heterogeneous in 16, and branching linear in one. The most common distribution of microcalcification was clustered (29 cases; 78.4%). Masses were oval or round in nine cases and irregular in three, and in seven cases their margin was ill-defined. In 13 cases, the density of the masses was equal to that of breast tissue. Ultrasonography showed that the masses were round or oval in 15 cases and irregular in 14, and that the margin was ill-defined in 16 cases and circumscribed in ten. In 19 cases, the echotexture of the masses was low, and in 20 cases, heterogeneous. Parallel orientation was seen in 25 cases, and ductal extension in 22. Category 4 was the most common final assessed BI

  11. Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55–74 years of age

    Science.gov (United States)

    Li, Christopher I.; Daling, Janet R.; Haugen, Kara L.; Tang, Mei Tzu Chen; Porter, Peggy L.; Malone, Kathleen E.

    2014-01-01

    Background The Women’s Health Initiative (WHI) randomized trials found that use of combined estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer risk, but use of unopposed estrogen hormone therapy (EHT) does not. However, several questions regarding the impact of hormone use on risk of different types of breast cancer and what thresholds of use confer elevations in risk remain. Methods We conducted a population-based case-control study among women 55–74 years of age to assess the association between menopausal hormone use and risk of invasive ductal and invasive lobular breast carcinomas. Associations were evaluated using polytomous logistic regression and analyses included 880 ductal cases, 1,027 lobular cases, and 856 controls. Results Current EHT and CHT use were associated with 1.6-fold [95% confidence interval (CI): 1.1–2.2] and 2.3-fold (95% CI: 1.7–3.2) increased risks of lobular breast cancer, respectively, but neither was associated with risk of ductal cancer. Lobular cancer risk was increased after nine years of EHT use, but after only three years of CHT use. Discussion Evidence across more than a dozen studies indicates that lobular carcinoma is the type of breast cancer most strongly influenced by menopausal hormones. Here we characterize what thresholds of duration of use of both EHT and CHT that confer elevations in risk. Impact Despite the rapid decline in hormone therapy use the WHI results were published, study of the hazards associated with these medications remains relevant given the estimated 38 million hormone therapy prescriptions that are still filled in the United States annually. PMID:24748570

  12. Five Year Outcome of 145 Patients With Ductal Carcinoma In Situ (DCIS) After Accelerated Breast Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ciervide, Raquel [Department of Radiation Oncology, New York University School of Medicine, NYU Langone Medical Center, New York, New York (United States); Dhage, Shubhada; Guth, Amber; Shapiro, Richard L.; Axelrod, Deborah M.; Roses, Daniel F. [Department of Surgery, New York University School of Medicine, NYU Langone Medical Center, New York, New York (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, NYU Langone Medical Center, New York, New York (United States)

    2012-06-01

    Background: Accelerated whole-breast radiotherapy (RT) with tumor bed boost in the treatment of early invasive breast cancer has demonstrated equivalent local control and cosmesis when compared with standard RT. Its efficacy in the treatment of ductal carcinoma in situ (DCIS) remains unknown. Methods and Materials: Patients treated for DCIS with lumpectomy and negative margins were eligible for 2 consecutive hypofractionated whole-breast RT clinical trials. The first trial (New York University [NYU] 01-51) prescribed to the whole breast 42 Gy (2.8 Gy in 15 fractions) and the second trial (NYU 05-181) 40.5 Gy (2.7 Gy in 15 fractions) with an additional daily boost of 0.5 Gy to the surgical cavity. Results: Between 2002 and 2009, 145 DCIS patients accrued, 59 to the first protocol and 86 to the second trial. Median age was 56 years and 65% were postmenopausal at the time of treatment. Based on optimal sparing of normal tissue, 79% of the patients were planned and treated prone and 21% supine. At 5 years' median follow-up (60 months; range 2.6-105.5 months), 6 patients (4.1%) experienced an ipsilateral breast recurrence in all cases of DCIS histology. In 3/6 patients, recurrence occurred at the original site of DCIS and in the remaining 3 cases outside the original tumor bed. New contralateral breast cancers arose in 3 cases (1 DCIS and 2 invasive carcinomas). Cosmetic self-assessment at least 2 years after treatment is available in 125 patients: 91% reported good-to-excellent and 9% reported fair-to-poor outcomes. Conclusions: With a median follow-up of 5 years, the ipsilateral local recurrence rate is 4.1%, comparable to that reported from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trials that employed 50 Gy in 25 fractions of radiotherapy for DCIS. There were no invasive recurrences. These results provide preliminary evidence that accelerated hypofractionated external beam radiotherapy is a viable option for DCIS.

  13. An unusual case of intracystic papillary carcinoma of breast with invasive component

    Directory of Open Access Journals (Sweden)

    Suryawanshi Kishor H, Nikumbh Dhiraj B, Damle Rajshri P, Dravid NV, Tayde Yogesh

    2014-07-01

    Full Text Available Papillary carcinoma of the breast is a rare malignant tumor, constituting 1-2 % of breast neoplasms mostly affecting elderly postmenopausal women. Intracystic (Encysted papillary carcinoma (IPC is a rare distinct entity with slow growth rate and overall favourable prognosis regardless of whether it is in situ alone or associated with invasive component. Treatment modalities vary from conservative surgery to radical surgery with or without adjuvant therapy depending upon the associated component (DCIS or invasive of the tumor. Herein, we report a case of 55-year-old female presented with a painless lump in the right breast. FNAC yielded haemorrhagic fluid with scanty cellularity of atypical ductal epithelial cells. Patient underwent wide local excision. The final histopathological diagnosis revealed intracystic papillary carcinoma associated with invasive ductal carcinoma, NOS type.

  14. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Solin, Lawrence J; Gray, Robert; Baehner, Frederick L; Butler, Steven M; Hughes, Lorie L; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Page, David L; Sledge, George W; Davidson, Nancy E; Ingle, James N; Perez, Edith A; Wood, William C; Sparano, Joseph A; Badve, Sunil

    2013-05-15

    For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. All statistical tests were two-sided. There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02). The DCIS Score quantifies IBE risk and invasive IBE risk, complements traditional clinical and pathologic factors, and provides a new clinical tool to improve selecting individualized treatment for women with DCIS who meet the ECOG E5194 criteria.

  15. Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?

    Directory of Open Access Journals (Sweden)

    Costarelli L

    2017-12-01

    Full Text Available Leopoldo Costarelli, Domenico Campagna, Alessandra Ascarelli, Francesco Cavaliere, Maria Helena Colavito, Tatiana Ponzani, Laura Broglia, Massimo La Pinta, Elena Manna, Lucio Fortunato Breast Unit, San Giovanni-Addolorata Hospital, Rome, Italy Background: Pleomorphic invasive lobular carcinoma (P-ILC is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.Materials and methods: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC and 574 cases of high-grade invasive ductal carcinoma (HG-IDC. We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.Results: P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway, its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.Conclusion: This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field. Keywords: breast cancer, lobular cancer, pleomorphic, mastectomy

  16. Pancreatic Ductal Adenocarcinoma (PDA) mice lacking Mucin 1 have a profound defect in tumor growth and metastasis

    Science.gov (United States)

    Besmer, Dahlia M.; Curry, Jennifer M.; Roy, Lopamudra D.; Tinder, Teresa L.; Sahraei, Mahnaz; Schettini, Jorge; Hwang, Sun-Il; Lee, Yong Y.; Gendler, Sandra J.; Mukherjee, Pinku

    2011-01-01

    MUC1 is over expressed and aberrantly glycosolated in >60% of pancreatic ductal adenocarcinomas. The functional role of MUC1 in pancreatic cancer has yet to be fully elucidated due to a dearth of appropriate models. In the present study, we have generated mouse models that spontaneously develop pancreatic ductal adenocarcinoma (KC), which are either Muc1-null (KCKO) or express human MUC1 (KCM). We show that KCKO mice have significantly slower tumor progression and rates of secondary metastasis, compared to both KC and KCM. Cell lines derived from KCKO tumors have significantly lower tumorigenic capacity compared to cells from KCM tumors. Therefore, mice with KCKO tumors had a significant survival benefit compared to mice with KCM tumors. In vitro, KCKO cells have reduced proliferation and invasion and failed to respond to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or matrix metalloproteinase-9 (MMP9). Further, significantly fewer KCKO cells entered the G2M phase of the cell cycle compared to the KCM cells. Proteomics and western blotting analysis revealed a complete loss of cdc-25c expression, phosphorylation of MAPK, as well as a significant decrease in Nestin and Tubulin α-2 chain expression in KCKO cells. Treatment with a MEK1/2 inhibitor, U0126, abrogated the enhanced proliferation of the KCM cells but had minimal effect on KCKO cells, suggesting that MUC1 is necessary for MAPK activity and oncogenic signaling. This is the first study to utilize a Muc1-null PDA mouse in order to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. PMID:21558393

  17. Impact of Boost Radiation in the Treatment of Ductal Carcinoma In Situ: A Population-Based Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rakovitch, Eileen, E-mail: Eileen.rakovitch@sunnybrook.ca [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada); Narod, Steven A. [University of Toronto, Toronto, Ontario (Canada); Women’s College Research Institute, Toronto, Ontario (Canada); Nofech-Moses, Sharon; Hanna, Wedad [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada); Thiruchelvam, Deva; Saskin, Refik; Taylor, Carole [Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Tuck, Alan [London Health Sciences Center, London, Ontario (Canada); Youngson, Bruce; Miller, Naomi; Done, Susan J. [University Health Network, Toronto, Ontario (Canada); Sengupta, Sandip [Kingston General Hospital, Kingston, Ontario (Canada); Elavathil, Leela [University of Toronto, Toronto, Ontario (Canada); Henderson General Hospital, 711 Concession Street, Hamilton, Ontario (Canada); Jani, Prashant A. [University of Toronto, Toronto, Ontario (Canada); Regional Health Sciences Centre, Thunder Bay, Ontario (Canada); Bonin, Michel [Sudbury Regional Hospital, Sudbury, Ontario (Canada); Metcalfe, Stephanie [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Paszat, Lawrence [Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); University of Toronto, Toronto, Ontario (Canada)

    2013-07-01

    Purpose: To report the outcomes of a population of women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and radiation and to evaluate the independent effect of boost radiation on the development of local recurrence. Methods and Materials: All women diagnosed with DCIS and treated with breast-conserving surgery and radiation therapy in Ontario from 1994 to 2003 were identified. Treatments and outcomes were identified through administrative databases and validated by chart review. The impact of boost radiation on the development of local recurrence was determined using survival analyses. Results: We identified 1895 cases of DCIS that were treated by breast-conserving surgery and radiation therapy; 561 patients received boost radiation. The cumulative 10-year rate of local recurrence was 13% for women who received boost radiation and 12% for those who did not (P=.3). The 10-year local recurrence-free survival (LRFS) rate among women who did and who did not receive boost radiation was 88% and 87%, respectively (P=.27), 94% and 93% for invasive LRFS (P=.58), and was 95% and 93% for DCIS LRFS (P=.31). On multivariable analyses, boost radiation was not associated with a lower risk of local recurrence (hazard ratio = 0.82, 95% confidence interval 0.59-1.15) (P=.25). Conclusions: Among a population of women treated with breast-conserving surgery and radiation for DCIS, additional (boost) radiation was not associated with a lower risk of local or invasive recurrence.

  18. Role of epithelial mesenchymal transition (EMT in pancreatic ductal adenocarcinoma (PDAC: is tumor budding the missing link?

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-09-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is <5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of epithelial-mesenchymal transition (EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.

  19. Prognostic Significance of Telomere Attrition in Ductal Carcinoma in Situ of the Breast

    National Research Council Canada - National Science Library

    Griffith, Jeffrey K

    2008-01-01

    We are using an innovative, quantitative assay for telomere DNA content (TC) developed and characterized by the PI, to test the hypothesis that TC predicts the likelihood of disease recurrence in women with ductal carcinoma in situ (DCIS...

  20. Impact of Margin Status on Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

    International Nuclear Information System (INIS)

    Childs, Stephanie K.; Chen, Yu-Hui; Duggan, Margaret M.; Golshan, Mehra; Pochebit, Stephen; Punglia, Rinaa S.; Wong, Julia S.; Bellon, Jennifer R.

    2013-01-01

    Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy. Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (≤2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy. Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (≤2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence. Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted

  1. Subclinical ductal carcinoma in situ of the breast: treatment with conservative surgery and radiotherapy.

    Science.gov (United States)

    Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Roncadin, M; Coghetto, F; Valdagni, R; Fasan, S; Maluta, S; Di Marco, A; Neri, S; Vidali, C; Panizzoni, G; Aristei, C

    1999-01-01

    In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

  2. Synergistic action of Smad4 and Pten in suppressing pancreatic ductal adenocarcinoma formation in mice.

    Science.gov (United States)

    Xu, X; Ehdaie, B; Ohara, N; Yoshino, T; Deng, C-X

    2010-02-04

    Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive. Using a Cre-LoxP approach, we generated a mutant mouse carrying a targeted deletion of Smad4 in the pancreas. We showed that the absence of Smad4 alone did not trigger pancreas tumor formation; however, it increased the expression of an inactivated form of Pten, suggesting a role of Pten in preventing Smad4-/- cells from undergoing malignancy. To investigate this, we disrupted both Pten and Smad4. We showed that Pten deficiency initiated widespread premalignant lesions, and a low tumor incidence that was significantly accelerated by Smad4-deficiency. The absence of Smad4 in a Pten-mutant background enhanced cell proliferation and triggered transdifferentiation from acinar, centroacinar and islet cells, accompanied by activation of Notch1 signaling. We showed that all tumors developed in the Smad4/Pten-mutant pancreas exhibited high levels of pAKT and mTOR, and that about 50 and 83% of human pancreatic cancers examined showed increased pAKT and pmTOR, respectively. Besides the similarity in gene expression, the pAKT and/or pmTOR-positive human PDACs and mouse pancreatic tumors also shared some histopathological similarities. These observations indicate that Smad4/Pten-mutant mice mimic the tumor progression of human pancreatic cancers that are driven by activation of the AKT-mTOR pathway, and uncovered a synergistic action of Smad4 and Pten in repressing pancreatic tumorigenesis.

  3. Correlation Between Expression of Twist and Podoplanin in Ductal Breast Carcinoma.

    Science.gov (United States)

    Grzegrzolka, Jedrzej; Wojtyra, Patrycja; Biala, Martyna; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Rys, Janusz; Podhorska-Okolow, Marzenna; Dziegiel, Piotr

    2017-10-01

    As a result of activation of transcription factors engaged in epithelial-mesenchymal transition (EMT), such as Twist, inhibition of epithelial markers and an increased expression of mesenchymal markers are observed. One of the specific markers of cancer-associated fibroblasts is podoplanin (PDPN) - a mucin-type membrane glycoprotein. The aim of this work was to study the localisation and intensity of expression of Twist and PDPN on the mRNA and protein level in cases of invasive ductal breast carcinoma (IDC), and its association with patients' clinico-pathological data. The study included archival material in a form of 80 paraffin IDC blocks and 11 IDC fragments frozen in liquid nitrogen. Immunohistochemical expression of Twist and PDPN was evaluated using light microscope and semiquantitative scale for evaluation of nuclear expression or immunoreactive scale (IRS) for evaluation of cytoplasmic expression. Material was isolated from frozen IDC fragments using laser micro-dissection (from cancer and stromal cells, separately) and was used to perform real-time PCR. Twist expression was higher in stromal cells in comparison to cancer cells. Analysis of patients' survival rate showed, that higher expression of Twist in cancer cells was associated with shorter overall survival time and shorter event-free survival time. The expression of PDPN was also higher in stromal cells in comparison with cancer cells. In addition, positive correlation was observed between expression of Twist and PDPN in stromal cells of IDC (r=0.267; p<0.05). The relationship between the higher expression of Twist in both cancer and stromal cells and shorter patients' survival indicates Twist as a potential useful prognostic marker in IDC. Positive correlation of Twist and PDPN expression may indicate the role of PDPN in EMT in IDC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Outcomes in Patients Treated With Mastectomy for Ductal Carcinoma In Situ

    International Nuclear Information System (INIS)

    Owen, Dawn; Tyldesley, Scott; Alexander, Cheryl; Speers, Caroline; Truong, Pauline; Nichol, Alan; Wai, Elaine S.

    2013-01-01

    Purpose: To examine, in a large, population-based cohort of women, the risk factors for recurrence after mastectomy for pure ductal carcinoma in situ (DCIS) and to identify which patients may benefit from postmastectomy radiation therapy. Methods and Materials: Data were analyzed for 637 subjects with pure DCIS, diagnosed between January 1990 and December 1999, treated initially with mastectomy. Locoregional relapse (LRR), breast cancer-specific survival, and overall survival were described using the Kaplan-Meier method. Reported risk factors for LRR (age, margins, size, Van Nuys Prognostic Index, grade, necrosis, and histologic subtype) were analyzed by univariate (log-rank) and multivariate (Cox modeling) methods. Results: Median follow-up was 12.0 years. Characteristics of the cohort were median age 55 years, 8.6% aged ≤40 years, 30.5% tumors >4 cm, 42.5% grade 3 histology, 37.7% multifocal disease, and 4.9% positive margins. At 10 years, LRR was 1.0%, breast cancer-specific survival was 98.0%, and overall survival was 90.3%. All recurrences (n=12) involved ipsilateral chest wall disease, with the majority being invasive disease (11 of 12). None of the 12 patients with recurrence died of breast cancer; all were successfully salvaged (median follow-up of 4.4 years). Ten-year LRR was higher with age ≤40 years (7.5% vs 1.5%; P=.003). Conclusion: Mastectomy provides excellent locoregional control for DCIS. Routine use of postmastectomy radiation therapy is not justified. Young age (≤40 years) predicts slightly higher LRR, but possibly owing to the small number of cases with multiple risk factors for relapse, a subgroup with a high risk of LRR (ie, approximately 15%) was not identified

  5. Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Ghassem-Zadeh, Sahar; Gaida, Matthias M; Szanyi, Szilard; Acha-Orbea, Hans; Frossard, Jean-Louis; Hinz, Ulf; Hackert, Thilo; Strobel, Oliver; Felix, Klaus

    2017-06-02

    Discriminating between autoimmune pancreatitis (AIP), chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) can be challenging. In this retrospective study, levels of serum and tissue cytokines were analyzed as part of the clinical strategy for the preoperative differentiation between AIP and PDAC. The identification of differential cytokine profiles may help to prevent unnecessary surgical resection and allow optimal treatment of these pathologies. To compare the cytokine profiles of AIP, CP, and PDAC patients, serum and pancreatic tissue homogenates were subjected to multiplex analysis of 17 inflammatory mediators. In total, serum from 73 patients, composed of 29 AIP (14 AIP-1 and 15 AIP-2), 17 CP, and 27 PDAC, and pancreatic tissue from 36 patients, including 12 AIP (six AIP-1 and six AIP-2), 12 CP, and 12 PDAC, were analyzed. Comparing AIP and PDAC patients' serum, significantly higher concentrations were found in AIP for interleukins IL-1β, IL-7, IL-13, and granulocyte colony-stimulating factor (G-CSF). G-CSF also allowed discrimination of AIP from CP. Furthermore, once AIP was divided into subtypes, significantly higher serum levels for IL-7 and G-CSF were measured in both subtypes of AIP and in AIP-2 for IL-1β when compared to PDAC. G-CSF and TNF-α were also significantly differentially expressed in tissue homogenates between AIP-2 and PDAC. The cytokines IL-1β, IL-7, and G-CSF can be routinely measured in patients' serum, providing an elegant and non-invasive approach for differential diagnosis. G-CSF is a good candidate to supplement the currently known serum markers in predictive tests for AIP and represents a basis for a combined blood test to differentiate AIP and particularly AIP-2 from PDAC, enhancing the possibility of appropriate treatment.

  6. MRI characteristics of ductal carcinoma in situ of the breast

    International Nuclear Information System (INIS)

    Xu Linghui; Peng Weijun; Gu Yajia; Li Ruimin; Liu Xiaohang; Wang Xiaohong; Mao Jian; Tang Feng; Ding Jianhui

    2011-01-01

    Objective: To evaluate and recognize the dynamic and morphological MRI characteristics of ductal carcinoma in situ (DCIS) of the breast and provide imaging information for the early detection and treatment planning. Methods: All MRI data in 71 patients with histologically proved DCIS were analyzed retrospectively. The 71 patients were divided into two groups, N1 (pure DCIS, 44 patients) and N2 (DCIS with microinvasion, 27 patients). According to the BI-RADS descriptors, all lesions were defined as a focus (smaller than 5 mm in diameter), mass and no-mass-like three enhancement types. The morphological features (M1 = focus, M2 =linear or linear-branched, M3 = branching-ductal, M4 = segmental, M5 = focal, M6 = regional, M7 = diffuse, M8 = mass) and the time-intensity curve (TIC) pattern [type Ⅰ (persistent enhancement curves), type Ⅱ (plateau), type Ⅲ (washout) and type Ⅳ (the same enhancement as glandular tissue)] were described. Chi-square test was used for the morphological characteristics of lesions. Results: The 73 DCIS lesions were found in 71 patients, and 5.5% (n=4) were stippled lesions, 87.7% (n=64) were no-mass like lesions, 6.8% (n=5) were mass-like lesions. In no-mass-like lesions (n= 64), M3 was found in 15 cases, M4 in 34 cases, M5 in 9 cases and M6 in 6 cases, respectively, M3 and M4 were the most common distribution patterns. In N1 group (n=45) and N2 group (n=28), M3, M4, M5, M6 were found in 7 and 8, 21 and 13, 7 and 2, 3 and 3 cases, respectively. There were no statistic differences between two groups (P>0.05). In 31 showed heterogeneous enhancement, both M3 and M4 were observed in 35.5% (11/31). In 26 clustered ring enhancement lesions, M4 was observed in 88.5% (23/26). Four lesions showed reticular enhancement, 2 lesions showed a clumped enhancement and 1 lesion showed homogeneous enhancement. In 5 mass-like lesions, N1 group had 3 cases, N2 group had 2 cases. Four lesions showed lobulated margin, 4 lesions showed speculated margin, 1

  7. Next generation sequencing of pancreatic ductal adenocarcinoma: right or wrong?

    Science.gov (United States)

    Connor, Ashton A; Gallinger, Steven

    2017-07-01

    Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all epithelial malignancies and a paradoxically rising incidence rate. Clinical translation of next generation sequencing (NGS) of tumour and germline samples may ameliorate outcomes by identifying prognostic and predictive genomic and transcriptomic features in appreciable fractions of patients, facilitating enrolment in biomarker-matched trials. Areas covered: The literature on precision oncology is reviewed. It is found that outcomes may be improved across various malignancies, and it is suggested that current issues of adequate tissue acquisition, turnaround times, analytic expertise and clinical trial accessibility may lessen as experience accrues. Also reviewed are PDAC genomic and transcriptomic NGS studies, emphasizing discoveries of promising biomarkers, though these require validation, and the fraction of patients that will benefit from these outside of the research setting is currently unknown. Expert commentary: Clinical use of NGS with PDAC should be used in investigational contexts in centers with multidisciplinary expertise in cancer sequencing and pancreatic cancer management. Biomarker directed studies will improve our understanding of actionable genomic variation in PDAC, and improve outcomes for this challenging disease.

  8. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

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    Louvrou Niki

    2008-04-01

    Full Text Available Abstract Background To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. Methods 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF, smooth muscle actin (SMA and CD34, while microvessel density (MVD was counted using the anti-CD31 antibody. Results VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p Conclusion Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.

  9. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast

    International Nuclear Information System (INIS)

    Zavagno, Giorgio; Capitanio, Giovanni; Ballarin, Andrea; Pierobon, Maria Elena; Marconato, Giorgia; Nitti, Donato; Carcoforo, Paolo; Marconato, Renato; Franchini, Zeno; Scalco, Giuliano; Burelli, Paolo; Pietrarota, Paolo; Lise, Mario; Mencarelli, Roberto

    2005-01-01

    Sentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial. The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS. A retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004. Subdermal or subareolar injection of 30–50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin. Only one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found. Our findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible

  10. Ductal carcinoma in situ of the breast (DCIS with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment

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    Fu Yuejiao

    2007-09-01

    Full Text Available Abstract Background Previously, 50% of patients with breast ductal carcinoma in situ (DCIS had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. Methods Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection, pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement, and 39 image features (morphology, densitometry, and texture. The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. Results Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with ~200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p Conclusion Image analysis provided reproducible assessments of nuclear features which quantitated differences in nuclear grading for patients. Quantitative nuclear image features indicated prognostically significant differences in DCIS, and may contribute additional information to prognostic assessments of which patients are likely to develop invasive disease.

  11. Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

    Science.gov (United States)

    Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

    2017-12-08

    Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci

  12. Morphologic classification of ductal breast tumors on ultrasound : differential diagnosis of benign and malignant tumors

    International Nuclear Information System (INIS)

    Won, Mi Sook; Chung, Soo Young; Yang, Ik; Lee, Yul; Park, Hai Jung; Lee, Myoung Hwan; Yoon, In Sook; Koh, Mi Gyoung

    1997-01-01

    To evaluate the morphologic differential diagnosis of benign and malignant ductal breast tumors, as seen on US US findings in 29 pathologically proven cases of ductal breast tumor were retrospectively reviewed. All patients were female and their mean age was 42 years. Nineteen tumors were benign and ten were malignant, and all ductal or cystic lesions showed solid masses. According to the location of the mural nodule, we classified the sonographic appearance of these tumors into three types:intraductal, intracystic and amorphic. The intraductal type was divided into three subtypes:incompletely obstructive, completely obstructive and multiple mural nodules. For the intracystic type, too, three subtypes were designated:the intracystic mural nodule (mural cyst), intracystic mural nodule with the duct (mural cyst+duct) and intracystic multiple mural nodules. The amorphic type is defined as an atypical ductal tumor with the mural nodule extending into adjacent parenchyma. The margin of the duct or cyst was smooth in 68.4% of benign, and irregular in 90% of malignant ductal tumors. Internal echogeneity of the duct or cyst usually showed homogeneity in both benign and malignant tumors. 73.7% of tumors connecting the duct were benign and 50% were malignant. In benign tumors, 52.6% of mural nodule had an irregular margin, while in malignant tumors, the corresponding proportion was 100%;both types usually showed heterogeneous hypoechogeneity. Among benign tumors, the most common morphologic type was the intraductal incompletely obstructive subtype (36.8%);among those that were malignant, the amorphic type was most common, accounting for 40% of tumors. No amorphic type was benign and no incompletely obstructive subtype was malignant. When ductal breast tumors are morphologically classified on the basis of sonographic findings, the intraductal incompletely obstructive subtype suggests benignancy, and the amorphic type, malignancy. The morphologic classification of ductal

  13. Overexpression of MMP-3 and uPA with Diminished PAI-1 Related to Metastasis in Ductal Breast Cancer Patients Attending a Public Hospital in Mexico City

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    Luis Miguel Barajas-Castañeda

    2016-01-01

    Full Text Available Extracellular matrix metalloproteases and the fibrinolytic system are important protease systems interacting with each other in charge of remodeling and recycling of tissues. Their role in tumor invasion and metastasis is often discussed. In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis. From the (118 primary tumors of Mexican patients with ductal breast cancer studied, 56% were grade II and 69% were size T2; the group with metastatic ganglia included 64 samples (54.3%. In patients with metastasis the estimated expression of MMP-3 and uPA (resp., 28% and 45% was higher than that from no metastatic tumors; it means there is higher expression of both markers in metastatic tumors (p<0.05. At the same time, metastatic tumors showed statistically significant lower signal of PAI-1 (24% than tumors without metastasis (p<0.05. We concluded that overexpression of MMP-3 and uPA, altogether with diminished expression of PAI-1 from metastatic tumors, might be a crucial step towards metastasis in ductal breast cancer. Nevertheless, additional studies in different populations are necessary to establish a pattern.

  14. DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Sun, Jie; Bi, Fangfang; Yang, Yang; Zhang, Yuan; Jin, Aihua; Li, Jinzi; Lin, Zhenhua

    2017-02-01

    DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

  15. Circular RNA Signature Predicts Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma

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    Feng Shao

    2018-06-01

    Full Text Available Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR cell lines and compared the circular RNAs (circRNAs profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Differentially expressed circRNAs were demonstrated using scatter plot and cluster heatmap analysis. Gene ontology and pathway analysis were performed to systemically map the genes which are functionally associated to those differentially expressed circRNAs identified from our data. The expression of the differentially expressed circRNAs picked up by RNAseq in PANC-1-GR cells was further validated by qRT-PCR and two circRNAs were eventually identified as the most distinct targets. Consistently, by analyzing plasma samples form pancreatic ductal adenocarcinoma (PDAC patients, the two circRNAs showed more significant expression in the Gemcitabine non-responsive patients than the responsive ones. In addition, we found that silencing of the two circRNAs could restore the sensitivity of PANC-1-GR cells to Gemcitabine treatment, while over-expression of them could increase the resistance of normal PANC-1 and MIA PACA-2 cells, suggesting that they might serve as drug targets for Gemcitabine resistance. Furthermore, the miRNA interaction networks were also explored based on the correlation analysis of the target microRNAs of these two circRNAs. In conclusion, we successfully established new PANC-1-GR cells, systemically characterized the circRNA and miRNA profiles, and identified two circRNAs as novel biomarkers and potential therapeutic targets for Gemcitabine non-responsive PDAC patients.

  16. Postoperative radiotherapy in salivary ductal carcinoma: a single institution experience

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    Kim, Tae Hyung; Kim, Mi Sun; Choi, Seo Hee; Suh, Yang Gun; Koh, Yoon Woo; Kim, Se Hun; Choi, Eun Chang; Keum, Ki Chang [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-15

    We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012. A total of 16 patients were identified and 15 eligible patients were included in analysis. Median age was 61 years (range, 40 to 71 years) and 12 patients (80%) were men. Twelve patients (80%) had a tumor in the parotid gland, 9 (60%) had T3 or T4 disease, and 9 (60%) had positive nodal disease. All patients underwent surgery and postoperative radiotherapy. Postoperative radiotherapy was delivered using 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Locoregional failure-free survival (LRFFS), distant failure-free survival (DFFS), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Differences in survival based on risk factors were tested using a log-rank test. Median total radiotherapy dose was 60 Gy (range, 52.5 to 63.6 Gy). Four patients received concurrent weekly chemotherapy with cisplatin. Among 10 patients who underwent surgery with neck dissection, 7 received modified radical neck dissection. With a median follow-up time of 38 months (range, 24 to 105 months), 4-year rates were 86% for LRFFS, 51% for DFFS, 46% for PFS, and 93% for OS. Local failure was observed in 2 patients (13%), and distant failure was observed in 7 (47%). The lung was the most common involved site of distant metastasis. Surgery and postoperative radiotherapy in SDC patients resulted in good local control, but high distant metastasis remained a major challenge.

  17. The diagnosis and management of pre-invasive breast disease: Pathological diagnosis – problems with existing classifications

    International Nuclear Information System (INIS)

    Van de Vijver, Marc J; Peterse, Hans

    2003-01-01

    In this review, we comment on the reasons for disagreement in the concepts, diagnosis and classifications of pre-invasive intraductal proliferations. In view of these disagreements, our proposal is to distinguish epithelial hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ, and to abandon the use of poorly reproducible categories, such as atypical ductal hyperplasia or ductal intraepithelial neoplasia, followed by a number to indicate the degree of proliferation and atypia, as these are not practical for clinical decision making, nor for studies aimed at improving the understanding of breast cancer development. If there is doubt about the classification of an intraductal proliferation, a differential diagnosis and the reason for and degree of uncertainty should be given, rather than categorizing a proliferation as atypical

  18. Epigenetic suppression of neprilysin regulates breast cancer invasion.

    Science.gov (United States)

    Stephen, H M; Khoury, R J; Majmudar, P R; Blaylock, T; Hawkins, K; Salama, M S; Scott, M D; Cosminsky, B; Utreja, N K; Britt, J; Conway, R E

    2016-03-07

    In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear. Here, we asked whether neprilysin expression predicts and functionally regulates breast cancer cell invasion. RT-PCR and flow cytometry analysis of MDA-MB-231 and MCF-7 breast cancer cell lines revealed decreased neprilysin expression compared with normal epithelial cells. Expression was also suppressed in invasive ductal carcinoma (IDC) compared with normal tissue. In addition, in vtro invasion assays demonstrated that neprilysin overexpression decreased breast cancer cell invasion, whereas neprilysin suppression augmented invasion. Furthermore, inhibiting neprilysin in MCF-7 breast cancer cells increased ET1 levels significantly, whereas overexpressing neprilysin decreased extracellular-signal related kinase (ERK) activation, indicating that neprilysin negatively regulates ET1-induced activation of mitogen-activated protein kinase (MAPK) signaling. To determine whether neprilysin was epigenetically suppressed in breast cancer, we performed bisulfite conversion analysis of breast cancer cells and clinical tumor samples. We found that the neprilysin promoter was hypermethylated in breast cancer; chemical reversal of methylation in MDA-MB-231 cells reactivated neprilysin expression and inhibited cancer cell invasion. Analysis of cancer databases revealed that neprilysin methylation significantly associates with survival in stage I IDC and estrogen receptor-negative breast cancer subtypes. These results demonstrate that neprilysin negatively regulates the ET axis in breast cancer

  19. Redefining Lumpectomy Using a Modification of the Sick Lobe Hypothesis and Ductal Anatomy

    International Nuclear Information System (INIS)

    Dooley, W.; Bong, J.; Parker, J

    2011-01-01

    Objectives. The Sick Lobe hypothesis states that breast cancers evolve from entire lobes or portions of lobes of the breast where initiation events have occurred early in development. The implication is that some cancers are isolated events and others are truly multi-focal but limited to single lobar-ductal units. Methods. This is a single surgeon retrospective review of early stage breast cancer lumpectomy patients treated from 1/2000 to 2/2005. Ductal endoscopy was used direct lumpectomy surgical margins by defining ductal anatomy and mapping proliferative changes within the sick lobe for complete excision. Results. Breast conservation surgery for stage 02 breast cancer with an attempt to perform endoscopy in association with therapeutic lumpectomy was performed in 554 patients (successful endoscopy in 465 cases). With an average followup of >5 years for the entire group, annual hazard rate for local failure in traditional lumpectomy without ductal mapping was 0.97%/yr. and for lumpectomy with ductal mapping and excision of entire sick lobe was 0.18%/yr. With endoscopy, 42% of patients were found to have extensive disease within their sick lobe. Conclusions. Targeting breast cancer lumpectomy using endoscopy and excision of regional associated proliferation seems associated with lower recurrence in this non-randomized series

  20. Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

    Science.gov (United States)

    Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

    2018-06-06

    Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

  1. Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment

    International Nuclear Information System (INIS)

    Chapman, Judith-Anne W; Miller, Naomi A; Lickley, H Lavina A; Qian, Jin; Christens-Barry, William A; Fu, Yuejiao; Yuan, Yan; Axelrod, David E

    2007-01-01

    Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection), pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement), and 39 image features (morphology, densitometry, and texture). The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with ~200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p < 0.001) associated with nuclear grading, and provided 78.8% correct jackknifed classification of a patient's nuclear grade. In multivariate assessments, image analysis nuclear features had significant prognostic associations (p ≤ 0.05) with the development of invasive breast cancer. Texture (difference entropy, p < 0.001; contrast, p < 0.001; peak transition probability, p = 0.01), densitometry (range density, p = 0.004), and measured margin (p = 0.05) were associated with

  2. A non-invasive modality: the US virtual touch tissue quantification (VTTQ) for evaluation of breast cancer.

    Science.gov (United States)

    Tamaki, Kentaro; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kano; Miyashita, Minoru; Ishida, Takanori; Sasano, Hironobu

    2013-09-01

    We evaluated the biologic features of breast tissues using a newly developed non-invasive diagnostic system, named virtual touch tissue quantification. A total of 180 patients including 115 invasive ductal carcinoma, 30 ductal carcinoma in situ, 4 mucinous carcinoma, 7 invasive lobular carcinoma, 8 fibroadenoma, 12 fibrocystic change and 4 intraductal papilloma were studied at Nahanishi Clinic, Okinawa. We first compared the results of virtual touch tissue quantification according to each histologic subtype and determined the optimal cutoff values for virtual touch tissue quantification to distinguish benign from malignant tissues, using the receiver operating characteristic method. In addition, we also examined the correlation between virtual touch tissue quantification velocities and Ki-67, estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 in cases of invasive ductal carcinoma using linear regression analyses and Student's t-test. Virtual touch tissue quantification velocities were statistically higher in malignant cases than in benign cases (P breast cancer pathology in a non-invasive fashion.

  3. Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

    OpenAIRE

    Haltas, Hacer; Bayrak, Reyhan; Yenidunya, Sibel; Kosehan, Dilek; Sen, Meral; Akin, Kayihan

    2012-01-01

    Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The ...

  4. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

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    Soroush Rais-Bahrami

    2017-01-01

    Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

  5. MR imaging of salivary glands after ductal ligation and stimulation by pilocarpine

    International Nuclear Information System (INIS)

    Patronas, N.J.; Tsuchimoch, M.; Webber, R.; Ruttimann, U.; Fox, P.; Bacher, J.; Schellinger, D.

    1988-01-01

    This paper presents an assessment of the usefulness of MR imaging in pathologic conditions of the salivary gland. The authors performed MR imaging in six dogs after ductal ligation on one side, followed by secretory stimulation with intraperitoneal injection of pilocarpine (5 mg/kg). On the images obtained after ductal ligation and before stimulation, there was no significant change in the signal intensity on either side. After injection of pilocarpine, however, T2-weighted images showed an obvious increase in signal intensity of the ligated gland in every instance. Their results indicate that MR images obtained after pilocarpine stimulation will be useful to study patients with ductal obstruction and that they may provide an objective basis for a noninvasive diagnostic test for unilateral stenosis

  6. Maintenance Therapy with Trastuzumab in Her2 Positive Metastatic Parotid Ductal Adenocarcinoma

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    Muhammad Shahid Iqbal

    2014-01-01

    Full Text Available Salivary ductal carcinomas (SDCs are extremely rare and aggressive malignancies, accounting for approximately 6% of all salivary gland malignancies. One distinct feature is their resemblance to ductal carcinomas of breast. A significant percentage of SDCs overexpress Her2 and the use of targeted therapy with trastuzumab can be considered in these patients. We report a rare case of long term disease control with trastuzumab in Her2 positive metastatic parotid ductal carcinoma. Our case also highlights that isolated brain metastasis should be managed aggressively to allow optimal local control when systemic disease is under remission with trastuzumab. We have also reviewed the published literature on the use of trastuzumab in SDCs.

  7. Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    Chen, Youdinghuan; Marotti, Jonathan D; Jenson, Erik G; Onega, Tracy L; Johnson, Kevin C; Christensen, Brock C

    2017-08-01

    The utility and reliability of assessing molecular biomarkers for translational applications on pre-operative core biopsy specimens assume consistency of molecular profiles with larger surgical specimens. Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. DNA was extracted from guided 2mm cores of formalin fixed paraffin embedded (FFPE) specimens, bisulfite-modified, and measured on the Illumina HumanMethylation450 BeadChip. DNA methylation profiles of core biopsies exhibited high concordance with matched surgical specimens. Within-subject variability in DNA methylation was significantly lower than between-subject variability (all Pcore biopsy and surgical specimens, 15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis by measurement of microRNA abundance in blood and tissue.

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    Andrea S Bauer

    Full Text Available A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC curves and the corresponding area under the curve (AUC analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875. Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer.

  9. Predictive values of BI-RADS® magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS)

    International Nuclear Information System (INIS)

    Badan, Gustavo Machado; Piato, Sebastião; Roveda, Décio; Faria Castro Fleury, Eduardo de

    2016-01-01

    Purpose: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Materials and methods: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Results: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. Conclusion: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases.

  10. Knowledge, satisfaction with information, decisional conflict and psychological morbidity amongst women diagnosed with ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    De Morgan, Simone; Redman, Sally; D'Este, Catherine; Rogers, Kris

    2011-07-01

    To assess knowledge, satisfaction with information, decisional conflict and psychological morbidity amongst women diagnosed with ductal carcinoma in situ (DCIS) and to explore the factors associated with less knowledge and greater confusion about DCIS. A cross-sectional survey of women diagnosed with DCIS in Australia (N=144). This study found misunderstanding and confusion amongst women diagnosed with DCIS and a desire for more information about their breast disease. Approximately half of participants worried about their breast disease metastasizing; approximately half expressed high decisional conflict; 12% were anxious and 2% were depressed. Logistic regression analysis demonstrated that worry about dying from the breast disease was significantly associated with not knowing that DCIS could not metastasize (OR 3.9; 95% CI 1.03-14.25); and confusion about whether DCIS could metastasize was significantly associated with dissatisfaction with information (OR 12.5; 95% CI 3.8-40.2). Good communication about how DCIS differs from invasive breast cancer is essential to alleviating the confusion and worry amongst women with DCIS. Recommendations about how best to communicate a diagnosis of DCIS, including the uncertainties, are needed to guide health professionals to promote better understanding about DCIS and increase the well-being of women with DCIS. Copyright © 2010. Published by Elsevier Ireland Ltd.

  11. Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, MA (United States); Sreedhara, Meera [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, MA (United States); Brock, Jane E., E-mail: jebrock@partners.org [Department of Pathology, Brigham and Women' s Hospital, Boston, MA (United States)

    2012-03-15

    Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2{sup +} DCIS. Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR{sup +}HER-2{sup -}, 27 were ER/PR{sup +}HER-2{sup +}, 6 were ER{sup -}/PR{sup -}HER-2{sup +}, and 6 were ER{sup -}/PR{sup -}HER-2{sup -}. On univariable analysis, HER-2{sup +}was significantly associated with Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2{sup +}. Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated

  12. Nuclear Morphometry in Ductal Breast Carcinoma with Correlation to Cell Proliferative Activity and Prognosis

    International Nuclear Information System (INIS)

    Radwan, M.M.; Amer, K.A.; Mokhtar, N.M.

    2003-01-01

    Morphometry is the quantitative description of biologic structures. This study was designed to evaluate the efficiency of morphometric measurements in diagnosis and prognosis of patients with breast carcinoma. Methods: Histological samples from 61 patients of invasive duct carcinoma (IDC) of no special type (NST), 12 cases of ductal carcinoma in situ (DCIS) and 14 control breast samples taken from fibrocystic change disease were retrospectively analyzed by computerized nuclear morphometry. All IDC patients underwent modified radical mastectomy without preoperative chemotherapy. The mean follow up was 28±19 months (range] -71). In each case, 25-50 nuclei were measured and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean maximum nuclear diameter (MMNO) and mean minimal nuclear diameter (Mmnd) were measured. The mean axis ratio (MAR), mean nuclear compactness (MNC), mean nuclear size (MNS) and mean shape factor (MSHF), were calculated mathematically. To measure the nuclear diameters, a new method was employed using the AutoCAD program. Morphometric parameters were compared with different clinico pathologic features, patient's survival and cell proliferative activity as determined by Ki-67 immunostaining which was evaluated quantitatively. Most of the morphometric parameters were significantly higher in DCIS and IDC groups than benign one. In IDC group morphometric features related to nuclear size (MNA, MNP, MMNO, Mmnd and MNS) were significantly correlated to most clinico pathologic features and cell proliferative activity assessed by Ki-67 immunostaining. However, the shape factor failed to achieve this correlation. The univariate analysis using Kaplan Meier curves indicated that short survival time was correlated with high nuclear morphometric values (MNA. MNP, MMND, Mmnd, MNS and MSHF). Moreover, the Spear man correlation analysis showed that Mmnd has the highest converse correlation with survival (r= -0.75, (ρ < 0.0001). In multivariate analysis

  13. Male ductal carcinoma in situ presenting as bloody nipple discharge: a case report and literature review.

    Science.gov (United States)

    Simmons, Rache M

    2002-01-01

    Male breast carcinoma accounts for 1% of all diagnosed breast carcinoma. Pure ductal carcinoma in situ in men is extremely rare. Unfortunately, male breast cancer is often diagnosed at a late stage because of the minimal awareness of presenting symptoms by the patient and sometimes by the health care provider. Because of this late presentation, the overall prognosis is less favorable. This case is presented to emphasize the importance of recognizing bloody nipple discharge as a clinical sign of male ductal carcinoma in situ and an opportunity for early diagnosis.

  14. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae

    2015-01-01

    that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

  15. Overexpression of SOX18 correlates with accelerated cell growth and poor prognosis in human pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Wang, Yazhou; Guo, Huahu; Zhang, Dafang; Yu, Xin; Leng, Xisheng; Li, Shu; Zhu, Weihua

    2016-01-01

    Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy. - Highlights: • Overexpression of SOX18 correlates with poor prognosis for pancreatic cancer. • SOX18 promotes pancreatic cancer cell growth in vitro and in vivo. • SOX18 promotes pancreatic cancer cell migration and invasion. • Knockdown of SOX18 induces G1/S phase arrest. • Knockdown of SOX18 induces decrease of cyclin D1, c-myc and MMP-7.

  16. Added Value of Breast MRI for Preoperative Diagnosis of Ductal Carcinoma In Situ: Diagnostic Performance on 362 Patients.

    Science.gov (United States)

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Triunfo, Flavia; Filice, Salvatore; Vallone, Paolo; Setola, Sergio Venanzio; Rubulotta, Mariarosaria; Di Bonito, Maurizio; Rinaldo, Massimo; D'Aiuto, Massimiliano; Brunetti, Arturo

    2017-06-01

    The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer. A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann-Whitney U, χ 2 test, and Spearman correlation coefficient were performed. The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade. Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Global genomic analysis of intraductal papillary mucinous neoplasms of the pancreas reveals significant molecular differences compared to ductal adenocarcinoma.

    Science.gov (United States)

    Fritz, Stefan; Fernandez-del Castillo, Carlos; Mino-Kenudson, Mari; Crippa, Stefano; Deshpande, Vikram; Lauwers, Gregory Y; Warshaw, Andrew L; Thayer, Sarah P; Iafrate, A John

    2009-03-01

    To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

  18. Flat epithelial atypia with and without atypical ductal hyperplasia: to re-excise or not. Results of a 5-year prospective study.

    Science.gov (United States)

    Uzoaru, Ikechukwu; Morgan, Bradley R; Liu, Zheng G; Bellafiore, Frank J; Gaudier, Farah S; Lo, Jeanne V; Pakzad, Kourosh

    2012-10-01

    Flat epithelial atypia (FEA) of the breast have a tendency to calcify and, as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3,948 cases of breast CNB between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. There were 3.7 % (145/3,948) pure FEA and 1.5 % (58/3,948) concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, 46.2 % (67/145) had microcalcifications on mammography with 65.5 % (95/145) of patients undergoing subsequent excisional biopsies with the following findings: benign 20 % (19/95), ADH 37.9 % (36/95), ductal carcinoma in situ (DCIS) 1.1 % (1/95), and DCIS and invasive ductal carcinoma (IDC) 2.1 % (2/95). In the concomitant FEA and ADH group, 86.2 % (50/58) patients had microcalcifications on radiograph with 74.1 % (43/58) of patients undergoing subsequent excisions with: benign 23.3 % (10/43), DCIS 9.3 % (4/43), DCIS and IDC 4.7 % (2/43), DCIS + lobular carcinoma in situ + invasive lobular carcinoma 2.3 % (1/43), and tubular carcinoma 2.3 % (1/43). The incidence of carcinoma in the FEA + ADH group is 18.6 % (8/43) and 3.2 % (3/95) for the pure FEA group. This difference is statistically significant (p = 0.0016). The relative risk of carcinoma in the ADH + FEA group versus the pure FEA group is 6.4773, with 95 % CI of 1.8432 and 22.76 24. Five-year mean follow-up in the unexcised pure FEA did not show any malignancies. These findings suggest that pure FEA has a very low association with carcinoma, and these patients may benefit from close clinical and mammographic follow-up while the combined pure FEA and ADH cases may be re-excised.

  19. Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases

    International Nuclear Information System (INIS)

    Cutuli, Bruno; De Lafontan, Brigitte; Kirova, Youlia; Auvray, Hugues; Tallet, Agnes; Avigdor, Sandrine; Brunaud, Claire; Delva, Catherine

    2015-01-01

    Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS. Two hundred patients with pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008. Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS) and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT) after BCS and 20 hormonal treatment (15 by tamoxifen). With a 144-month median follow-up (FU), there were no local recurrences (LR) among 24 patients treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5% at 10 years). No specific LR risk factors were identified. Three patients developed metastases, two after invasive LR; 22 patients (11%) developed contralateral BC (59% invasive) and another five had second cancer. LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS). The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR. BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS

  20. Mammogram synthesis using a three-dimensional simulation. III. Modeling and evaluation of the breast ductal network

    International Nuclear Information System (INIS)

    Bakic, Predrag R.; Albert, Michael; Brzakovic, Dragana; Maidment, Andrew D. A.

    2003-01-01

    A method is proposed for realistic simulation of the breast ductal network as part of a computer three-dimensional (3-D) breast phantom. The ductal network is simulated using tree models. Synthetic trees are generated based upon a description of ductal branching by ramification matrices (R matrices), whose elements represent the probabilities of branching at various levels of a tree. We simulated the ductal network of the breast, consisting of multiple lobes, by random binary trees (RBT). Each lobe extends from the ampulla and consists of branching ductal segments of decreasing size, and the associated terminal ductal-lobular units. The lobes follow curved paths that project from the nipple toward the chest wall. We have evaluated the RBT model by comparing manually- traced ductal networks from 25 projections of ductal lobes in clinical galactograms and manually- traced networks from 23 projections of synthetic RBTs. A root-mean-square (rms) fractional error of 41%, between the R-matrix elements corresponding to clinical and synthetic images, was computed. This difference was influenced by projection and segmentation artifacts and by the limited number of available images. In addition, we analyzed 23 synthetic trees generated using R matrices computed from clinical images. A comparison of these synthetic and clinical images yielded a rms fractional error of 11%, suggesting the possibility that a more appropriate model of the ductal branching morphology may be developed. Rejection of the RBT model also suggests the existence of a relationship between ductal branching morphology and the state of mammary development and pathology

  1. MR features to suggest microinvasive ductal carcinoma of the breast: can it be differentiated from pure DCIS?

    International Nuclear Information System (INIS)

    Hahn, Soo Yeon; Han, Boo-Kyung; Ko, Eun Young; Shin, Jung Hee; Nam, Meeyoung; Hwang, Ji-Young

    2013-01-01

    Background: Morphologic and kinetic characteristics of breast lesions are regarded as a major criterion for their differential diagnosis in dynamic magnetic resonance imaging (MRI). However, there have not been well-reported MRI findings of microinvasive ductal carcinoma. Purpose: To evaluate MRI characteristics of microinvasive ductal carcinoma of the breast and to compare MRI findings in patients with microinvasive ductal carcinoma and pure ductal carcinoma in situ (DCIS). Material and Methods: Eighty-one patients with pathologically confirmed microinvasive ductal carcinomas (n = 37) or pure DCIS (n = 44) were included in this study. The MRI findings were analyzed without knowledge of the pathologic and conventional imaging findings. For all the lesions detected on MRI, morphologic and kinetic analyses were performed according to the Breast Imaging Reporting and Data System. For the non-mass lesions, the presence of clustered ring enhancement was also analyzed. Statistical analyses were performed using Student's t test, χ 2 test, and Fisher's exact test. Results: In total 35 cases of microinvasive ductal carcinoma and 39 cases of DCIS were detected on MRI. The most common and dominant MRI findings of microinvasive ductal carcinoma and DCIS were non-mass lesions with heterogeneous enhancement. However, the spiculated margin of the mass-type lesion (P = 0.022), the segmental distribution (P = 0.023), and clustered ring enhancement (P = 0.006) of the non-mass-type lesion, and the enhancement kinetics showing strong initial enhancement (P = 0.004) with subsequent wash-out (P = 0.001) were significantly more frequent in microinvasive ductal carcinoma than in DCIS. Conclusion: Non-mass lesions with segmental distribution, heterogeneous enhancement, and strong initial enhancement with a wash-out curve were the dominant MRI findings of microinvasive ductal carcinoma. Compared with DCIS, microinvasive ductal carcinoma showed more suspicious imaging characteristics. For

  2. Tamoxifen added to radiotherapy and surgery for the treatment of ductal carcinoma in situ of the breast: A meta-analysis of 2 randomized trials

    International Nuclear Information System (INIS)

    Petrelli, Fausto; Barni, Sandro

    2011-01-01

    Background: Surgical excision with adequate margins is the treatment of choice for ductal, in situ carcinoma of the breast (DCIS). The addition of radiotherapy (RT) halved local in situ and invasive recurrence. The purpose of our meta-analysis is to evaluate the reduction in recurrence (in situ or invasive) with the addition of tamoxifen (T), in particular in patients with DCIS treated with surgery + RT. Patients and methods: The eligible studies (NSABP-B24 and UK ANZ DCIS trials) included prospective, randomized, controlled trials in which the addition of T had been compared with surgery + RT without T in women with DCIS of the breast. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for both in situ and invasive recurrence (local and controlateral). Results: Tamoxifen does not reduce breast cancer-specific or overall mortality when added to loco-regional therapy for DCIS of the breast (surgery plus or minus RT). Tamoxifen reduces overall breast cancer recurrence by 29% in all patients and by 33% in those treated with both surgery and RT. Only ipsilateral invasive (RR 0.61 [95% CI 0.41, 0.92]; p = 0.02) and controlateral in situ relapses (RR 0.40 [95% CI 0.16, 0.96]; p = 0.04) are significantly lowered when T is added to RT. Tamoxifen seems to exert a local synergistic effect with RT. Both young and older women ( 50 years) achieve some benefit from the addition of T (RR 0.6 and 0.74, respectively). Conclusion: The addition of T to surgery and RT for DCIS of the breast reduces the risk of local invasive and controlateral in situ relapses, but not the survival. The benefit is independent of age. In conclusion, surgery associated with RT and T is the treatment of choice for patients with (estrogen-receptor positive) DCIS of the breast.

  3. Long-term survival of women with basal-like ductal carcinoma in situ of the breast: a population-based cohort study

    International Nuclear Information System (INIS)

    Zhou, Wenjing; Jirström, Karin; Johansson, Christine; Amini, Rose-Marie; Blomqvist, Carl; Agbaje, Olorunsola; Wärnberg, Fredrik

    2010-01-01

    Microarray gene-profiling of invasive breast cancer has identified different subtypes including luminal A, luminal B, HER2-overexpressing and basal-like groups. Basal-like invasive breast cancer is associated with a worse prognosis. However, the prognosis of basal-like ductal carcinoma in situ (DCIS) is still unknown. Our aim was to study the prognosis of basal-like DCIS in a large population-based cohort. All 458 women with a primary DCIS diagnosed between 1986 and 2004, in Uppland and Västmanland, Sweden were included. TMA blocks were constructed. To classify the DCIS tumors, we used immunohistochemical (IHC) markers (estrogen-, progesterone-, HER2, cytokeratin 5/6 and epidermal growth factor receptor) as a surrogate for the gene expression profiling. The association with prognosis was examined for basal-like DCIS and other subtypes using Kaplan-Meier survival analyses and Cox proportional hazards regression models. IHC data were complete for 392 women. Thirty-two were basal-like (8.2%), 351 were luminal or HER2-positive (89.5%) and 9 unclassified (2.3%). Seventy-six women had a local recurrence of which 34 were invasive. Another 3 women had general metastases as first event. Basal-like DCIS showed a higher risk of local recurrence and invasive recurrence 1.8 (Confidence interval (CI) 95%, 0.8-4.2) and 1.9 (0.7-5.1), respectively. However, the difference was not statistically significant. Also, no statistically significant increased risk was seen for triple-negative or high grade DCIS. Basal-like DCIS showed about a doubled, however not statistically significant risk for local recurrence and developing invasive cancer compared with the other molecular subtypes. Molecular subtyping was a better prognostic parameter than histopathological grade

  4. International variation in management of screen-detected ductal carcinoma in situ of the breast

    DEFF Research Database (Denmark)

    Ponti, Antonio; Lynge, Elsebeth; James, Ted

    2014-01-01

    BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evalu...

  5. Solitary main pancreatic ductal calculus of possible biliary origin causing acute pancreatitis.

    Science.gov (United States)

    Chaparala, Ramakrishna Prasad Chowdary; Patel, Rafiuddin; Guthrie, James Ahsley; Davies, Mervyn Huw; Guillou, Pierre J; Menon, Krishna V

    2005-09-10

    Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. A 59-year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) revealed a calculus in the main pancreatic duct in the head of the pancreas causing acute pancreatitis. There were no features suggestive of chronic pancreatitis on CT scanning. The episode acute pancreatitis was managed conservatively. ERCP extraction of the calculus failed as the stone was impacted in the main pancreatic duct resulting in severe acute pancreatitis. Once this resolved, a transduodenal exploration and extraction of the pancreatic ductal calculus was performed successfully. Crystallographic analysis revealed the composition of the calculus was different to that seen in chronic pancreatitis, but more in keeping with a calculus of biliary origin. This could be explained by migration of the biliary calculus via the common channel into the main pancreatic duct. Following the operation the patient made an uneventful recovery and was well at two-year follow up. Acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Failing endoscopic extraction, transduodenal exploration and extraction is a safe option after resolution of acute pancreatitis.

  6. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

    necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

  7. Pain, Sensory Disturbances, and Psychological Distress among Danish Women Treated for Ductal Carcinoma In Situ

    DEFF Research Database (Denmark)

    Mertz, Birgitte Goldschmidt; Duriaud, Helle M; Kroman, Niels

    2017-01-01

    of diagnosis decreasing to 10% after 12 months. Similarly 36% of breast cancer patients reported distress at time of diagnosis and 10% after 12 months. Interviews confirmed that ductal carcinoma in situ patients experienced distress and also uncovered physical problems and rehabilitation needs. The study...

  8. Electron microscopic study of the spilt irradiation effects on the rat parotid ductal cells

    International Nuclear Information System (INIS)

    Kim, Sung Soo; Lee, Sang Rae

    1988-01-01

    This study was designed to investigate the effects of split irradiation on the salivary ductal cells, especially on the intercalated cells of the rat parotid glands. For this study, 24 Sprague-Dawley strain rats were irradiated on the head and neck region with two equal split doses of 9 Gy for a 4 hours interval by Co-60 teletherapy unit, Picker's mode l 4M 60. The conditions of irradiation were that field size, dose rate, SSD and depth were 12 X 5 cm, 222 cGy/min, 50 cm and 1 cm, respectively. The experimental animals were sacrificed 1, 2, 3, 6, 12, hours and 1, 3, 7, days after the irradiation and the changes of the irradiated intercalated cells of the parotid glands were examined under light and electron microscope. The results were as follows: 1. By the split irradiation, the degenerative changes of intercalated cells of the parotid glands appeared at 3 hours after irradiation and the most severe cellular degeneration observed at 6 hours after irradiation. The repair processes began from 12 hours after irradiation and have matured progressively. 2. Under electron microscope, loss of nuclear membrane, microvilli and secretory granules, derangement of chromosomes, degeneration of cytoplasm, atrophy or reduction of intracytoplasmic organelles were observed in the intercalated ductal cells after split irradiation. 3. Under light microscope, derangement of ductal cells, widening of cytoplasms and nuclei, hyperchromatism and proliferation of ductal cells were observed in intercalated ducts after split irradiation.

  9. Interfacing polymeric scaffolds with primary pancreatic ductal adenocarcinoma cells to develop 3D cancer models

    NARCIS (Netherlands)

    Ricci, C.; Mota, C.M.; Moscato, S.; D' Alessandro, D.; Ugel, S.; Sartoris, S.; Bronte, V.; Boggi, U.; Campani, D.; Funel, N.; Moroni, Lorenzo; Danti, S.

    2014-01-01

    We analyzed the interactions between human primary cells from pancreatic ductal adenocarcinoma (PDAC) and polymeric scaffolds to develop 3D cancer models useful for mimicking the biology of this tumor. Three scaffold types based on two biocompatible polymeric formulations, such as poly(vinyl

  10. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

    NARCIS (Netherlands)

    Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; de Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A.; Tuveson, David A.; Capunzo, Mario; Karin, Michael; de Laurenzi, Vincenzo; Turco, Maria Caterina

    2015-01-01

    The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of

  11. Ductal Mucus Obstruction and Reduced Fluid Secretion Are Early Defects in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Anita Balázs

    2018-05-01

    Full Text Available Objective: Defective mucus production in the pancreas may be an important factor in the initiation and progression of chronic pancreatitis (CP, therefore we aimed to (i investigate the qualitative and quantitative changes of mucus both in human CP and in an experimental pancreatitis model and (ii to correlate the mucus phenotype with epithelial ion transport function.Design: Utilizing human tissue samples and a murine model of cerulein induced CP we measured pancreatic ductal mucus content by morphometric analysis and the relative expression of different mucins in health and disease. Pancreatic fluid secretion in CP model was measured in vivo by magnetic resonance cholangiopancreatography (MRCP and in vitro on cultured pancreatic ducts. Time-changes of ductal secretory function were correlated to those of the mucin production.Results: We demonstrate increased mucus content in the small pancreatic ducts in CP. Secretory mucins MUC6 and MUC5B were upregulated in human, Muc6 in mouse CP. In vivo and in vitro fluid secretion was decreased in cerulein-induced CP. Analysis of time-course changes showed that impaired ductal ion transport is paralleled by increased Muc6 expression.Conclusion: Mucus accumulation in the small ducts is a combined effect of mucus hypersecretion and epithelial fluid secretion defect, which may lead to ductal obstruction. These results suggest that imbalance of mucus homeostasis may have an important role in the early-phase development of CP, which may have novel diagnostic and therapeutic implications.

  12. Sox9b is a key regulator of pancreaticobiliary ductal system development.

    Directory of Open Access Journals (Sweden)

    Marion Delous

    Full Text Available The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the

  13. A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis.

    Science.gov (United States)

    Nealon, William H; Bhutani, Manoop; Riall, Taylor S; Raju, Gottumukkala; Ozkan, Orhan; Neilan, Ryan

    2009-05-01

    Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications.

  14. Effects of large pressure amplitude low frequency noise in the parotid gland perivasculo-ductal connective tissue.

    Science.gov (United States)

    Oliveira, Pedro; Brito, José; Mendes, João; da Fonseca, Jorge; Águas, Artur; Martins dos Santos, José

    2013-01-01

    In tissues and organs exposed to large pressure amplitude low frequency noise fibrosis occurs in the absence of inflammatory signs, which is thought to be a protective response. In the parotid gland the perivasculo-ductal connective tissue surrounds arteries, veins and the ductal tree. Perivasculo-ductal connective tissue is believed to function as a mechanical stabilizer of the glandular tissue. In order to quantify the proliferation of perivasculo-ductal connective tissue in large pressure amplitude low frequency noise-exposed rats we used sixty Wistar rats which were equally divided into 6 groups. One group kept in silence, and the remaining five exposed to continuous large pressure amplitude low frequency noise: g1-168h (1 week); g2-504h (3 weeks); g3-840h (5 weeks); g4-1512h (9 weeks); and g5-2184h (13 weeks). After exposure, parotid glands were removed and the perivasculo-ductal connective tissue area was measured in all groups. We applied ANOVA statistical analysis, using SPSS 13.0. The global trend is an increase in the average perivasculo-ductal connective tissue areas, that develops linearly and significantly with large pressure amplitude low frequency noise exposure time (p connective tissue. Hence, these results show that in response to large pressure amplitude low frequency noise exposure, rat parotid glands increase their perivasculo-ductal connective tissue.

  15. pH Regulatory Transporters in Pancreatic Ductal Adenocarcinoma

    DEFF Research Database (Denmark)

    Kong, Su Chii

    The abnormal features of hypoxia and altered metabolisms in solid tumours lead to an increased glycolysis that is uncoupled from oxidative phosphorylation in the TCA cycle. Tumoural cells often exhibit dysregulated expressions and activities of various membrane pH regulatory transporters to cope...... with the elevated acid production from this glycolysis, as well as from cellular ATP hydrolysis, sequentially creating a favourable intracellular pH and hostile acidic tumour microenvironment, fortify the tumour cells with highly invasive, metastatic and drug resistant phenotype. In current work, we study...... proliferation was found to be decreased while apoptosis was increased with concanamycin A treatment, indicative of V-ATPases being involved in PDAC cell survival mechanisms as well. Comprehending pH regulation in tumour cells might provide insights in preventing tumourigenesis by pH disruptions. Data presented...

  16. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    International Nuclear Information System (INIS)

    Abasolo, Ibane; Pujal, Judit; Navarro, Pilar; Rabanal, Rosa M.; Serafin, Anna; Millan, Olga; Real, Francisco X.

    2009-01-01

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  17. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)

    2009-07-15

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  18. Invasive lobular breast cancer: the prognostic impact of histopathological grade, E-cadherin and molecular subtypes.

    Science.gov (United States)

    Engstrøm, Monica J; Opdahl, Signe; Vatten, Lars J; Haugen, Olav A; Bofin, Anna M

    2015-02-01

    The aim of this study was to compare breast cancer specific survival (BCSS) for invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and, further, to evaluate critically the prognostic value of histopathological grading of ILC and examine E-cadherin as a prognostic marker in ILC. The study comprised 116 lobular and 611 ductal breast carcinomas occurring between 1961 and 2008. All cases had been classified previously according to histopathological type and grade, stained for oestrogen receptor (ER), progesterone receptor (PR), antigen Ki67 (Ki67), epithelial growth factor receptor (EGFR), cytokeratin 5 (CK5) and human epidermal growth factor receptor 2 (HER2) and classified into molecular subtypes. For the present study, immunohistochemical staining for E-cadherin was performed. The Kaplan-Meier method and Cox proportional hazards models were used in the analyses. Grade 2 tumours comprised 85.3% of the lobular tumours and 51.9% of the ductal tumours. BCSS in ILC grade 2 was comparable to that of IDC grade 3. E-cadherin-negative ILC had a poorer prognosis compared to E-cadherin positive ILC and to IDC regardless of E-cadherin status. The implication of histopathological grading may differ in ILC compared to IDC. E-cadherin may be useful in prognostication in ILC and thereby influence the determination of treatment strategies for this group of women. © 2014 The Authors. Histopathology published by John Wiley & Sons Ltd.

  19. Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS)

    International Nuclear Information System (INIS)

    Fowble, B.; Hanlon, A.L.; Fein, D.A.; Hoffman, J.P.; Sigurdson, E.R.; Patchefsky, A.; Kessler, H.

    1996-01-01

    Purpose: The role of conservative surgery and radiation for mammographically detected DCIS is controversial. In particular, there is a paucity of data for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographically detected DCIS ≤2.5 cm, negative resection margins, negative post-biopsy mammogram). The purpose of this study is to report long term outcome of conservative surgery and radiation for mammographically detected DCIS with emphasis on the results in patients (pts.) considered candidates for excision alone. Materials and Methods: From 1983 to 1992, 110 women with mammographically detected DCIS (calcifications 72%, mass ± calcifications 27%) and no prior history of breast cancer underwent needle localization biopsy followed by radiation. The median age of the patient population was 56 yrs. (range 37-81). The median followup was 5.3 yrs. (range .5-12). Re-excision was performed in 55%. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. Axillary dissection was performed in 31 pts. and all had negative nodes. 31% had a positive family history of breast cancer (1 affected relative-25 pts., two-7 pts., three-2 pts.). The most common predominant histologic subtype was comedo (54%) followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). A post-biopsy mammogram prior to radiation was performed in 46% of the patients. Radiation consisted of treatment to the entire breast (median 5000 cGy) with a boost to the primary site (97%) of an additional 1000 cGy. The median total dose to the primary site was 6040 cGy (range 5000 to 6660). Results: Three patients developed a recurrence in the treated breast at 52, 106, and 107 months. All 3 recurrences were invasive ductal cancers and all were treated with mastectomy. The location of the recurrence was in the same quadrant as the primary in 1 pt. and in a separate quadrant in 2 pts

  20. Breast ductal lavage for biomarker assessment in high risk women: rationale, design and methodology of a randomized phase II clinical trial with nimesulide, simvastatin and placebo

    International Nuclear Information System (INIS)

    Lazzeroni, Matteo; Radice, Davide; Bonanni, Bernardo; Guerrieri-Gonzaga, Aliana; Serrano, Davide; Cazzaniga, Massimiliano; Mora, Serena; Casadio, Chiara; Jemos, Costantino; Pizzamiglio, Maria; Cortesi, Laura

    2012-01-01

    Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. From 2005 to 2011, 150 women with a history of estrogen receptor negative ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible procedure, the treatment is well tolerated

  1. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  2. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  3. Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Haltas Hacer

    2012-08-01

    Full Text Available Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744

  4. Cost-effectiveness of radiation therapy following conservative surgery for ductal carcinoma in situ of the breast

    International Nuclear Information System (INIS)

    Suh, W. Warren; Hillner, Bruce E.; Pierce, Lori J.; Hayman, James A.

    2005-01-01

    Purpose: To assess the cost-effectiveness of radiation therapy (RT) in patients with ductal carcinoma in situ (DCIS) after breast-conserving surgery (BCS). Methods and materials: A Markov model was constructed for a theoretical cohort of 55-year-old women with DCIS over a life-time horizon. Probability estimates for local noninvasive (N-INV), local invasive (INV), and distant recurrences were obtained from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17. Utilities for eight nonmetastatic health states were collected from both healthy women and DCIS patients. Direct medical (2002 Medicare fee schedule) and nonmedical costs (time and transportation) of RT were ascertained. Results: For BCS + RT vs. BCS alone, the estimated N-INV and INV rates at 12 years were 9% and 8% vs. 16% and 18%, respectively. The incremental cost of adding RT was $3300 despite an initial RT cost of $8700 due to higher local recurrence-related salvage costs incurred with the BCS alone strategy. An increase of 0.09 quality-adjusted life-years (QALYs) primarily reflected the lower risk of INV with RT, resulting in an incremental cost-effectiveness ratio (ICER) of $36,700/QALY. Sensitivity analyses revealed the ICER to be affected by baseline probability of a local recurrence, relative efficacy of RT in preventing INV, negative impact of an INV on quality of life, and cost of initial RT. Cost of salvage BCS + RT and source of utilities (healthy women vs. DCIS patients) influenced the ICER albeit to a lesser degree. Conclusions: Addition of RT following BCS for patients with DCIS should not be withheld because of concerns regarding its cost-effectiveness

  5. Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

    Science.gov (United States)

    Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Arcicasa, M; Coghetto, F; Valdagni, R; Maluta, S; Di Marco, A

    1997-09-01

    The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

  6. Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Liu, Hung-Yi; Korc, Murray; Lin, Chien-Chi

    2018-04-01

    The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT). Copyright © 2018 Elsevier Ltd. All rights

  7. HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis

    International Nuclear Information System (INIS)

    Chile, Thais; Bacchella, Telésforo; Giorgi, Ricardo Rodrigues; Fortes, Maria Angela Henriques Zanella; Corrêa-Giannella, Maria Lúcia Cardillo; Brentani, Helena Paula; Maria, Durvanei Augusto; Puga, Renato David; Paula, Vanessa de Jesus R de; Kubrusly, Marcia Saldanha; Novak, Estela Maria

    2013-01-01

    Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated. Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively. Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquitin-dependent catabolic process and cell cycle. The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies

  8. Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia 1

    OpenAIRE

    Pitarresi, Jason R.; Liu, Xin; Sharma, Sudarshana M.; Cuiti?o, Maria C.; Kladney, Raleigh D.; Mace, Thomas A.; Donohue, Sydney; Nayak, Sunayana G.; Qu, Chunjing; Lee, James; Woelke, Sarah A.; Trela, Stefan; LaPak, Kyle; Yu, Lianbo; McElroy, Joseph

    2016-01-01

    Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2) was elevated in smooth muscle actin?positive fibroblasts in the stroma of pancreatic ductal adenocarcinoma (PDAC) patient tissue...

  9. [Comparison of laparoscopic distal pancreatectomy and open distal pancreatectomy in pancreatic ductal adenocarcinoma].

    Science.gov (United States)

    Xu, K; Su, J J; Su, M; Yan, L; Feng, J; Xin, X L; Chen, Y L

    2017-10-23

    Objective: To compare and evaluate the curative effect of laparoscopic distal pancreatectomy(LDP) and traditional open distal pancreatectomy(ODP) in pancreatic ductal adenocarcinoma. Methods: The clinical data of 15 patients treated by LDP and 87 contemporaneous cases treated by ODP from January 2010 to November 2015 was collected, and the curative effect and prognosis of these patients were retrospectively analyzed. Results: The operation time of LDP group was (286.5±48.1) min, significantly longer than that of OPD group(226.6±56.8) min ( P 0.05). In both LDP group and ODP group, none occurred percutaneous drainage, re-admissions, second operation or perioperative death. Conclusions: Compared to ODP, LDP is much safer and more steady in perioperative periodand operation. Patients of pancreatic ductal adenocarcinoma received LDP can acquire more benefit and recovery sooner, and LDP is a safe and effective operative method.

  10. Two cases of chronic pancreatitis associated with anomalous pancreaticobiliary ductal union and SPINK1 mutation

    Directory of Open Access Journals (Sweden)

    Eun Sam Rho

    2013-05-01

    Full Text Available Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine&#8211;protease inhibitor, Kazal type 1 (SPINK1 , cationic trypsinogen (PRSS1 , and cystic fibrosis&#8211;transmembrane conductance regulator (CFTR genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU. However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.

  11. Ductal carcinoma in situ within fibroadenoma: Microcalcifications identified on mammography play a crucial role in diagnosis

    International Nuclear Information System (INIS)

    You, Jai Kyung; Kim, Yee Jeong; Kim, Bo Mi; Kim, Eun Kyung

    2016-01-01

    Fibroadenoma is a common, benign tumor of the breast, which is rarely associated with an increased risk of carcinoma. We report a case of ductal carcinoma in situ within a fibroadenoma in a 38-year-old woman. The lesion was a 1 cm, circumscribed, ovoid mass with internal calcifications evident on mammography and ultrasound, which is commonly found in fibroadenoma, but the calcifications were fine and linear, which is uncommon. This type of calcification is classified as suspicious by the American College of Radiology Breast Imaging-Reporting And Data System, and it is often correlated with comedo necrosis of ductal carcinoma, and, so, requires immediate pathologic confirmation. In our case, careful analysis of the unusual calcifications led to appropriate intervention and diagnosis. Radiologists should be aware that fibroadenomas can be malignant, and they should look for suspicious microcalcifications within a fibroadenoma

  12. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast

    Directory of Open Access Journals (Sweden)

    Liu Yan-Xue

    2009-04-01

    Full Text Available Abstract Background Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported. Case presentation A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma. Conclusion In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects.

  13. Ductal carcinoma in situ within fibroadenoma: Microcalcifications identified on mammography play a crucial role in diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    You, Jai Kyung; Kim, Yee Jeong; Kim, Bo Mi [NHIS Ilsan Hospital, Goyang (Korea, Republic of); Kim, Eun Kyung [Dept. of Diagnostic Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Fibroadenoma is a common, benign tumor of the breast, which is rarely associated with an increased risk of carcinoma. We report a case of ductal carcinoma in situ within a fibroadenoma in a 38-year-old woman. The lesion was a 1 cm, circumscribed, ovoid mass with internal calcifications evident on mammography and ultrasound, which is commonly found in fibroadenoma, but the calcifications were fine and linear, which is uncommon. This type of calcification is classified as suspicious by the American College of Radiology Breast Imaging-Reporting And Data System, and it is often correlated with comedo necrosis of ductal carcinoma, and, so, requires immediate pathologic confirmation. In our case, careful analysis of the unusual calcifications led to appropriate intervention and diagnosis. Radiologists should be aware that fibroadenomas can be malignant, and they should look for suspicious microcalcifications within a fibroadenoma.

  14. Apocrine Sweat Gland Ductal Adenoma with Sebaceous Differentiation in a Dog

    Directory of Open Access Journals (Sweden)

    Masaki Michishita

    2013-01-01

    Full Text Available A 7-year-old male, Border Collie, developed a firm mass, measuring approximately 1 cm in diameter, in the left buccal skin. Histologically, the mass was composed of ductal structures lined by bilayered luminal epithelial and basaloid tumor cells along with a few nests of sebaceous cells. Immunohistochemical staining revealed that the luminal epithelial tumor cells were positive for cytokeratin (CK, CAM5.2 and CK19 but not for CK14 or p63. In contrast, the basaloid tumor cells were positive for CK14, p63, and αSMA but not for CK19 or CAM5.2. CK8 expression was observed in both luminal epithelial and basaloid tumor cells. The tumor cells with sebaceous differentiation were positive for CK14 but not for the other markers. This is the first case of an apocrine sweat gland ductal adenoma with sebaceous differentiation occurring in the buccal skin of a dog.

  15. A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.

    OpenAIRE

    Jeran K Stratford; David J Bentrem; Judy M Anderson; Cheng Fan; Keith A Volmar; J S Marron; Elizabeth D Routh; Laura S Caskey; Jonathan C Samuel; Channing J Der; Leigh B Thorne; Benjamin F Calvo; Hong Jin Kim; Mark S Talamonti; Christine A Iacobuzio-Donahue

    2010-01-01

    Editors' Summary Background Pancreatic cancer kills nearly a quarter of a million people every year. It begins when a cell in the pancreas (an organ lying behind the stomach that produces digestive enzymes and hormones such as insulin, which controls blood sugar levels) acquires genetic changes that allow it to grow uncontrollably and to spread around the body (metastasize). Nearly all pancreatic cancers are “pancreatic ductal adenocarcinomas” (PDACs)—tumors that start in the cells that line ...

  16. Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

    OpenAIRE

    Pour, P. M.; Weide, L.; Liu, G.; Kazakoff, K.; Scheetz, M.; Toshkov, I.; Ikematsu, Y.; Fienhold, M. A.; Sanger, W.

    1997-01-01

    To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinog...

  17. ERP in chronic pancreatitis - ductal morphology, relation to exocrine function and pain - clinical value

    International Nuclear Information System (INIS)

    Norup Lauridsen, K.; Raahede, J.; Kruse, A.; Thommesen, P.; Aarhus Univ.

    1985-01-01

    ERP was analyzed in 87 patients with chronic pancreatitis with special reference to its clinical value in management of pain, the dominating symptom in uncomplicated chronic pancreatitis. A significant correlation was found between ductal changes due to pancreatitis and decrease in pancreatic function. However, no association was found between severe pancreatic pain and pancreatic function or pancreatic morphology. The significance of ERP in management of patients with persistent severe pancreatic pain is discussed. (orig.) [de

  18. SMAD4 Loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells

    OpenAIRE

    Chen, Yu-Wen; Hsiao, Pi-Jung; Weng, Ching-Chieh; Kuo, Kung-Kai; Kuo, Tzu-Lei; Wu, Deng-Chyang; Hung, Wen-Chun; Cheng, Kuang-Hung

    2014-01-01

    Background SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully c...

  19. Ductal Carcinoma In Situ Detected by Shear Wave Elastography within a Fibroadenoma

    OpenAIRE

    Kılıç, Fahrettin; Ustabaşıoğlu, Fethi Emre; Samancı, Cesur; Baş, Ahmet; Velidedeoglu, Mehmet; Kılıçaslan, Tülin; Aydogan, Fatih; Yılmaz, Mehmet Halit

    2014-01-01

    Fibroadenoma is the most common breast tumor in women. Malignant transformation occurs rarely within fibroadenoma at older ages. Clinicians, radiologists, and pathologists need to be aware of malignant transformation within fibroadenomas. Radiologic studies play an important role in the diagnosis of fibroadenoma; however, radiologic findings are often nonspecific for malignancy and may appear completely benign. We detected an occult ductal carcinoma in situ that originated inside a fibroadeno...

  20. The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Pedersen, Stine Helene Falsig; Novak, Ivana

    2015-01-01

    of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour. METHODS: We determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human...

  1. Mechanisms of Transendothelial Migration of Primary Human Invasive Ductal Carcinoma Cells from ER+, Her2+, and Triple-Negative Disease

    Science.gov (United States)

    2016-09-01

    expressing vascular endothelial cells; M, CD68-expressing macrophages. Scale bars, 300 mm (left) and 50 mm (right). (B and C) Scatter plots of relative...by low-power scanning using the following criteria: high density of tumor, adequacy of tumor, lack of necrosis or inflammation, and lack of artifacts...marker of metastatic outcome in patients1–5. Each TMEM site is comprised of a Mena over-expressing tumor cell, a peri- vascular macrophage and an

  2. Poorly differentiated ductal adenocarcinoma of the pancreas with rapid progression in a young man.

    Science.gov (United States)

    Tezuka, Koji; Ishiyama, Tomoharu; Takeshita, Akiko; Matsumoto, Hidekazu; Jingu, Akira; Kikuchi, Jiro; Yamaya, Hideyuki; Ohe, Rintaro; Ishizawa, Tetsuya

    2018-04-16

    Pancreatic cancer in young adults is very rare. We report a case of young-onset poorly differentiated pancreatic ductal adenocarcinoma with rapid progression and poor prognosis in a 31-year-old Japanese man with no obvious family history of malignancy. Preoperative examinations revealed a mass lesion in the body of the pancreas, accompanied by a slightly dilated main pancreatic duct distal to the mass lesion. Pancreatic cancer with acute pancreatitis was suspected because of an elevation of serum pancreatic enzyme and tumor marker, along with imaging findings. Distal pancreatectomy with resection of the common hepatic artery and splenectomy along with lymph node dissection was performed. Microscopically, the tumor was mainly composed of poorly differentiated ductal adenocarcinoma. The postoperative course was uneventful, but the patient had multiple liver metastases 2 months postoperatively, in spite of adjuvant chemotherapy, and died 8 months postoperatively. This case may represent a rare instance of young-onset poorly differentiated ductal adenocarcinoma with rapid progression and may indicate potential risk factors of pancreatic cancer in young adults.

  3. Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

    Science.gov (United States)

    Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

    2013-11-19

    Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

  4. Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

    Science.gov (United States)

    Limaiem, F; Khadhar, A; Hassan, F; Bouraoui, S; Lahmar, A; Mzabi, S

    2013-12-01

    A 77-year-old female patient with a medical history significant for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola tender mass with irregular borders associated with mild right nipple retraction. Mammography showed a 2.2 x 2.4 cm stellate mass of the right breast. Ultrasound-guided core biopsies of the tumour were performed. Pathological examination revealed a grade II infiltrating ductal carcinoma. The patient underwent right radical mastectomy with homolateral axillary lymphadenectomy. Histological examination of the surgical specimen revealed grade II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis. To the best of our knowledge, the coexistence of granulomatous lobular mastitis and ductal carcinoma has been described only twice in the English language literature. The theory that chronic inflammation leads to cancer is well documented. Whether our patient had developed cancer from granulomatous lobular mastitis or otherwise is a matter of debate until more cases are encountered and more research is done in the area of breast cancer pathogenesis with regards to it arising from granulomatous lobular mastitis.

  5. The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

    International Nuclear Information System (INIS)

    Pavlakis, Kitty; Messini, Irene; Vrekoussis, Thomas; Yiannou, Petros; Keramopoullos, Dimitrios; Louvrou, Niki; Liakakos, Theodoros; Stathopoulos, Efstathios N

    2008-01-01

    To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma

  6. Cytologic features of nipple aspirate fluid using an automated non-invasive collection device: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Rowe Leslie R

    2005-08-01

    Full Text Available Abstract Background Detection of cytologic atypia in nipple aspirate fluid (NAF has been shown to be a predictor of risk for development of breast carcinoma. Manual collection of NAF for cytologic evaluation varies widely in terms of efficacy, ease of use, and patient acceptance. We investigated a new automated device for the non-invasive collection of NAF in the office setting. Methods A multi-center prospective observational clinical trial involving asymptomatic women designed to assess fluid production, adequacy, safety and patient acceptance of the HALO NAF Collection System (NeoMatrix, Irvine, CA. Cytologic evaluation of all NAF samples was performed using previously described classification categories. Results 500 healthy women were successfully enrolled. Thirty-eight percent (190/500 produced fluid and 187 were available for cytologic analysis. Cytologic classification of fluid producers showed 50% (93/187 Category 0 (insufficient cellular material, 38% (71/187 Category I (benign non-hyperplastic ductal epithelial cells, 10% (18/187 Category II (benign hyperplastic ductal epithelial cells, 3% (5/187 Category III (atypical ductal epithelial cells and none were Category IV (unequivocal malignancy. Overall, 19% of the subjects produced NAF with adequate cellularity and 1% were found to have cytologic atypia. Conclusion The HALO system is a simple, safe, rapid, automated method for standardized collection of NAF which is acceptable to patients. Cytologic assessment of HALO-collected NAF showed the ability to detect benign and pre-neoplastic ductal epithelial cells from asymptomatic volunteers.

  7. Conservative treatment of breast ductal carcinoma in situ: results of an Italian multi-institutional retrospective study

    International Nuclear Information System (INIS)

    Vidali, Cristiana; Neri, Stefano; Pietta, Nicoletta; Caffo, Orazio; Aristei, Cynthia; Bertoni, Filippo; Bonetta, Alberto; Guenzi, Marina; Iotti, Cinzia; Leonardi, Maria Cristina; Mussari, Salvatore

    2012-01-01

    The incidence of ductal carcinoma in situ (DCIS) has increased markedly in recent decades. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery followed by radiation therapy (RT) has become the standard approach. We present the final results of a multi-institutional retrospective study of an Italian Radiation Oncology Group for the study of conservative treatment of DCIS, characterized by a very long period of accrual, from February 1985 to March 2000, and a median follow-up longer than 11 years. A collaborative multi-institutional study was conducted in Italy in 10 Radiation Oncology Departments. A consecutive series of 586 women with DCIS histologically confirmed, treated between February 1985 and March 2000, was retrospectively evaluated. Median age at diagnosis was 55 years (range: 29–84); 32 patients were 40 years old or younger. All women underwent conservative surgery followed by whole breast RT. Irradiation was delivered to the entire breast, for a median total dose of 50 Gy; the tumour bed was boosted in 295 cases (50%) at a median dose of 10 Gy. After a median follow-up of 136 months (range: 16–292 months), 59/586 patients (10%) experienced a local recurrence: invasive in 37 cases, intraductal in 20 and not specified in two. Salvage mastectomy was the treatment of choice in 46 recurrent patients; conservative surgery in 10 and it was unknown in three patients. The incidence of local recurrence was significantly higher in women younger than 40 years (31.3%) (p= 0.0009). Five patients developed distant metastases. Furthermore 40 patients developed a contralateral breast cancer and 31 a second primary tumour in a different site. The 10-year actuarial overall survival (OS) was 95.5% and the 10-year actuarial disease-specific survival (DSS) was 99%. Our results are consistent with those reported in the literature. In particular it has been defined the importance of young age (40

  8. Breast-conserving surgery with or without radiotherapy in women with ductal carcinoma in situ: a meta-analysis of randomized trials

    Directory of Open Access Journals (Sweden)

    Leon Paola G

    2007-08-01

    Full Text Available Abstract Background To investigate whether Radiation therapy (RT should follow breast conserving surgery in women with ductal carcinoma in situ from breast cancer (DCIS with objective of decreased mortality, invasive or non invasive recurrence, distant metastases and contralateral breast cancer rates. We have done a meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision. Methods A meta-analysis of randomized controlled trials (RCT was performed comparing RT treatment for DCIS of breast cancer to observation. The MEDLINE, EMBASE, CANCERLIT, Cochrane Library databases, Trial registers, bibliographic databases, and recent issues of relevant journals were searched. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria. Results The reviewers identified four large RCTs, yielding 3665 patients. Pooled results from this four randomized trials of adjuvant radiotherapy showed a significant reduction of invasive and DCIS ipsilateral breast cancer with odds ratio (OR of 0.40 (95% CI 0.33 – 0.60, p Conclusion The conclusion from our meta-analysis is that the addition of radiation therapy to lumpectomy results in an approximately 60% reduction in breast cancer recurrence, no benefit for survival or distant metastases compared to excision alone. Patients with high-grade DCIS lesions and positive margins benefited most from the addition of radiation therapy. It is not yet clear which patients can be successfully treated with lumpectomy alone; until further prospective studies answer this question, radiation should be recommended after lumpectomy for all patients without contraindications.

  9. The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

    Science.gov (United States)

    van Luijt, P A; Heijnsdijk, E A M; Fracheboud, J; Overbeek, L I H; Broeders, M J M; Wesseling, J; den Heeten, G J; de Koning, H J

    2016-05-10

    The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

  10. Outcome and prognostic factors for local recurrence in mammographically detected ductal carcinoma in situ of the breast treated with conservative surgery and radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    White, Julia; Levine, Alan; Gustafson, Gregory; Wimbish, Kathryn; Ingold, John; Pettinga, Jane; Matter, Richard; Martinez, Alvaro; Vicini, Frank

    1995-02-15

    Purpose: We have retrospectively reviewed our institution's experience treating a predominantly mammographically detected population of ductal carcinoma in situ (DCIS) patients with conservative surgery and radiation therapy (CSRT) to determine outcome and prognostic factors for local recurrence. Methods and Materials: Between January 1, 1982 and December 31, 1988, 52 consecutive cases of DCIS of the breast were treated with CSRT at William Beaumont Hospital. Forty-six (88%) were mammographically detected nonpalpable lesions. All patients underwent at least an excisional biopsy and 28 (54%) were reexcised. The axilla was surgically staged in 41 (79%) and all were N0. The entire breast was irradiated to 45-50 Gy over 5-6 weeks. The tumor bed was boosted in 49 (94%) so that the minimum dose was 60 Gy. The three patients not boosted received a minimum dose of 50 Gy to the entire breast. Pathologic materials were reviewed by one of the authors. Results: The predominant DCIS pattern was comedo in 40%, cribriform in 28%, solid in 17%, and micropapillary in 15%. The predominant nuclear grade was Grade I in 51%, Grade II in 49%, and Grade III in 0%. The median follow-up is 68 months. There have been three recurrences in the treated breast at a median time to failure of 30 months. The 5- and 8-year actuarial local recurrence rate is 6%. One patient recurred with invasive ductal cancer at 28 months, and the other two recurrences were DCIS at 30 and 50 months. All three patients were treated with salvage mastectomy. The patient who recurred locally with an invasive cancer developed metastasis and died at 64 months. The 5- and 8-year actuarial cause-specific survival rates are 100% and 97%, respectively. The following pathologic factors were analyzed for an association with local recurrence: predominant DCIS histology, predominant nuclear grade, and highest nuclear grade. Of these, the predominant nuclear grade was the best predictor of local recurrence (p = 0.070). No

  11. Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

    2016-01-01

    In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

  12. Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience

    International Nuclear Information System (INIS)

    Cutuli, Bruno; Cohen-Solal-le Nir, Christine; Lafontan, Brigitte de; Mignotte, Herve; Fichet, Virginie; Fay, Renaud; Servent, Veronique; Giard, Sylvia; Charra-Brunaud, Claire; Lemanski, Claire; Auvray, Hugues; Jacquot, Stephane; Charpentier, Jean-Christophe

    2002-01-01

    Purpose: To assess the long-term outcome for women with ductal carcinoma in situ of the breast treated in current clinical practice by conservative surgery with or without definitive breast irradiation. Methods and Materials: We analyzed 705 cases of ductal carcinoma in situ treated between 1985 and 1995 in nine French regional cancer centers; 515 underwent conservative surgery and radiotherapy (CS+RT) and 190 CS alone. The median follow-up was 7 years. Results: The 7-year crude local recurrence (LR) rate was 12.6% (95% confidence interval [CI] 9.4-15.8) and 32.4% (95% CI 25-39.7) for the CS+RT and CS groups, respectively (p<0.0001). The respective 10-year results were 18.2% (95% CI 13.3-23) and 43.8% (95% CI 30-57.7). A total of 125 LRs occurred, 66 and 59 in the CS+RT and CS groups, respectively. Invasive or microinvasive LRs occurred in 60.6% and 52% of the cases in the same respective groups. The median time to LR development was 55 and 41 months. Nine (1.7%) and 6 (3.1%) nodal recurrences occurred in the CS+RT and CS groups, respectively. Distant metastases occurred in 1.4% and 3% of the respective groups. Patient age and excision quality (final margin status) were both significantly associated with LR risk in the CS+RT group: the LR rate was 29%, 13%, and 8% among women aged ≤40, 41-60, and ≥61 years (p<0.001). Even in the case of complete excision, we observed a 24% rate of LR (6 of 25) in women <40 years. Patients with negative, positive, or uncertain margins had a 7-year crude LR rate of 9.7%, 25.2%, and 12.2%, respectively (p=0.008). RT reduced the LR rate in all subgroups, especially in those with comedocarcinoma (17% vs. 59% in the CS+RT and CS groups, respectively, p<0.0001) and mixed cribriform/papillary tumors (9% vs. 31%, p<0.0001). In the multivariate Cox regression model, young age and positive margins remained significant in the CS+RT group (p=0.00012 and p=0.016). Finally, the relative LR risk in the CS+RT group compared with the CS group

  13. Aberrant E-cadherin staining patterns in invasive mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Brogi Edi

    2005-11-01

    Full Text Available Abstract Background E-cadherin, a cell surface protein involved in cell adhesion, is present in normal breast epithelium, benign breast lesions, and in breast carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function. Inactivation of E-cadherin in lobular carcinomas and certain diffuse gastric carcinomas may play a role in the dispersed, discohesive "single cell" growth patterns seen in these tumors. The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin protein expression as evidenced by immunohistochemistry, whereas ductal carcinomas are typically E-cadherin positive. Patients and methods We report on E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma Results These were five exceptional instances in which the E-cadherin immunophenotype did not correspond to the apparent histologic classification of the lesion. These cases which are exceedingly rare in our experience are the subject of this report. Conclusion Findings such as those illustrated in this study occur in virtually all biologic phenomena and they do not invalidate the very high degree of correlation between the expression of E-cadherin and the classification of breast carcinomas as ductal or lobular type on the basis of conventional histologic criteria.

  14. Second primary pancreatic ductal carcinoma in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma: High cumulative incidence rates at 5 years after pancreatectomy.

    Science.gov (United States)

    Ishida, Jun; Toyama, Hirochika; Matsumoto, Ippei; Asari, Sadaki; Goto, Tadahiro; Terai, Sachio; Nanno, Yoshihide; Yamashita, Azusa; Mizumoto, Takuya; Ueda, Yuki; Kido, Masahiro; Ajiki, Tetsuo; Fukumoto, Takumi; Ku, Yonson

    2016-01-01

    The aim of this study was to determine the incidence rate and clinical features of second primary pancreatic ductal carcinoma (SPPDC) in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma (PDC). Data of patients undergoing R0 resection for PDC at a single high-volume center were reviewed. SPPDC was defined as a tumor in the remnant pancreas after R0 resection for PDC, and SPPDC met at least one of the following conditions: 1) the time interval between initial pancreatectomy and development of a new tumor was 3 years or more; 2) the new tumor was not located in contact with the pancreatic stump. We investigated the clinical features and treatment outcomes of patients with SPPDC. This study included 130 patients who underwent surgical resection for PDC between 2005 and 2014. Six (4.6%) patients developed SPPDC. The cumulative 3- and 5-year incidence rates were 3.1% and 17.7%, respectively. Four patients underwent remnant pancreatectomy for SPPDC. They were diagnosed with the disease in stage IIA or higher and developed recurrence within 6 months after remnant pancreatectomy. One patient received carbon ion radiotherapy and survived 45 months. One patient refused treatment and died 19 months after the diagnosis of SPPDC. The incidence rate of SPPDC is not negligible, and the cumulative 5-year incidence rate of SPPDC is markedly high. Post-operative surveillance of the remnant pancreas is critical for the early detection of SPPDC, even in long-term survivors after PDC resection. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line

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    Zhang, Leshuai W.; McMahon Tobin, Grainne A.; Rouse, Rodney L., E-mail: rodney.rouse@fda.hhs.gov

    2012-10-15

    The glucagon-like peptide 1 receptor (GLP1R) plays a critical role in glucose metabolism and has become an important target for a growing class of drugs designed to treat type 2 diabetes. In vitro studies were designed to investigate the effect of the GLP1R agonist, exenatide (Ex4), in “on-target” RIN-5mF (islet) cells as well as in “off-target” AR42J (acinar) and DSL-6A/C1 (ductal) cells in a diabetic environment. Ex4 increased islet cell proliferation but did not affect acinar cells or ductal cells at relevant concentrations. A high caloric, high fat diet is a risk factor for impaired glucose tolerance and type-2 diabetes. An in vitro Oleic acid (OA) model was used to investigate the effect of Ex4 in a high calorie, high fat environment. At 0.1 and 0.4 mM, OA mildly decreased the proliferation of all pancreatic cell types. Ex4 did not potentiate the inhibitory effect of OA on cell proliferation. Akt phosphorylation in response to Ex4 was diminished in OA-treated ductal cells. GLP1R protein detected by western blot was time and concentration dependently decreased after glucose stimulation in OA-treated ductal cells. In ductal cells, OA treatment altered the intracellular localization of GLP1R and its co-localization with early endosome and recycling endosomes. Chloroquine (lysosomal inhibitor), N-acetyl-L-cysteine (reactive oxygen species scavenger) and wortmannin (a phosphatidylinositol-3-kinase inhibitor), fully or partially, rescued GLP1R protein in OA-pretreated, glucose-stimulated ductal cells. The impact of altered regulation on phenotype/function is presently unknown. However, these data suggest that GLP1R regulation in ductal cells can be altered by a high fat, high calorie environment. -- Highlights: ► Exenatide did not inhibit islet, acinar or ductal cell proliferation. ► GLP1R protein decreased after glucose stimulation in oleic acid-treated ductal cells. ► Oleic acid treatment altered localization of GLP1R with early and recycling

  16. Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line

    International Nuclear Information System (INIS)

    Zhang, Leshuai W.; McMahon Tobin, Grainne A.; Rouse, Rodney L.

    2012-01-01

    The glucagon-like peptide 1 receptor (GLP1R) plays a critical role in glucose metabolism and has become an important target for a growing class of drugs designed to treat type 2 diabetes. In vitro studies were designed to investigate the effect of the GLP1R agonist, exenatide (Ex4), in “on-target” RIN-5mF (islet) cells as well as in “off-target” AR42J (acinar) and DSL-6A/C1 (ductal) cells in a diabetic environment. Ex4 increased islet cell proliferation but did not affect acinar cells or ductal cells at relevant concentrations. A high caloric, high fat diet is a risk factor for impaired glucose tolerance and type-2 diabetes. An in vitro Oleic acid (OA) model was used to investigate the effect of Ex4 in a high calorie, high fat environment. At 0.1 and 0.4 mM, OA mildly decreased the proliferation of all pancreatic cell types. Ex4 did not potentiate the inhibitory effect of OA on cell proliferation. Akt phosphorylation in response to Ex4 was diminished in OA-treated ductal cells. GLP1R protein detected by western blot was time and concentration dependently decreased after glucose stimulation in OA-treated ductal cells. In ductal cells, OA treatment altered the intracellular localization of GLP1R and its co-localization with early endosome and recycling endosomes. Chloroquine (lysosomal inhibitor), N-acetyl-L-cysteine (reactive oxygen species scavenger) and wortmannin (a phosphatidylinositol-3-kinase inhibitor), fully or partially, rescued GLP1R protein in OA-pretreated, glucose-stimulated ductal cells. The impact of altered regulation on phenotype/function is presently unknown. However, these data suggest that GLP1R regulation in ductal cells can be altered by a high fat, high calorie environment. -- Highlights: ► Exenatide did not inhibit islet, acinar or ductal cell proliferation. ► GLP1R protein decreased after glucose stimulation in oleic acid-treated ductal cells. ► Oleic acid treatment altered localization of GLP1R with early and recycling

  17. DEGRO practical guidelines: radiotherapy of breast cancer II. Radiotherapy of non-invasive neoplasia of the breast

    International Nuclear Information System (INIS)

    Souchon, R.; Sautter-Bihl, M.L.; Sedlmayer, F.; Budach, W.; Dunst, J.; Feyer, P.; Fietkau, R.; Sauer, R.; Harms, W.; Wenz, F.; Haase, W.

    2014-01-01

    To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were ''non invasive breast cancer'', ''ductal carcinoma in situ, ''dcis'', ''borderline breast lesions'', ''lobular neoplasia'', ''radiotherapy'' and ''radiation therapy''. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50?% of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly

  18. Role of cytologic grading in prognostication of invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Khan Nazoora

    2009-01-01

    noninvasive, cytologic grading is comparable to histologic grading and might provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting mode of therapy and to predict tumor behavior.

  19. Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

    2014-01-01

    Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

  20. Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer

    International Nuclear Information System (INIS)

    Sim, Y.T.; Vinnicombe, S.; Whelehan, P.; Thomson, K.; Evans, A.

    2015-01-01

    Aim: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. Materials and methods: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. Results: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). Conclusion: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious. - Highlights: • Sensitivity of shear-wave elastography (SWE) for detecting lobular cancers is 94%. • Sensitivity of SWE for detecting invasive ductal cancers is 100%. • SWE is more sensitive than mammography for detecting ductal and lobular cancers. • SWE can diagnose ILC as suspicious, which are benign/normal on conventional imaging

  1. Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies

    Directory of Open Access Journals (Sweden)

    Heger Christopher D

    2010-12-01

    Full Text Available Abstract Background Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers. Methods Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses. Results We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76% of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72% and 27% had only low levels of expression. Conclusions Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in

  2. Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans.

    Science.gov (United States)

    Pour, P. M.; Weide, L.; Liu, G.; Kazakoff, K.; Scheetz, M.; Toshkov, I.; Ikematsu, Y.; Fienhold, M. A.; Sanger, W.

    1997-01-01

    To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined had the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9176407

  3. Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center experience.

    Science.gov (United States)

    Zhang, Ai-Bin; Wang, Ye; Hu, Chen; Shen, Yan; Zheng, Shu-Sen

    2017-06-01

    The aim of this study was to compare complications and oncologic outcomes of patients undergoing laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP) at a single center. Distal pancreatectomies performed for pancreatic ductal adenocarcinoma during a 4-year period were included in this study. A retrospective analysis of a database of this cohort was conducted. Twenty-two patients underwent LDP for pancreatic ductal adenocarcinoma, in comparison to seventy-six patients with comparable tumor characteristics treated by ODP. No patients with locally advanced lesions were included in this study. Comparing LDP group to ODP group, there were no significant differences in operation time (P=0.06) or blood loss (P=0.24). Complications (pancreatic fistula, P=0.62; intra-abdominal abscess, P=0.44; postpancreatectomy hemorrhage, P=0.34) were similar. There were no significant differences in the number of lymph nodes harvested (11.2±4.6 in LDP group vs. 14.4±5.5 in ODP group, P=0.44) nor the rate of patients with positive lymph nodes (36% in LDP group vs. 41% in ODP group, P=0.71). Incidence of positive margins was similar (9% in LDP group vs. 13% in ODP group, P=0.61). The mean overall survival time was (29.6±3.7) months for the LDP group and (27.6±2.1) months for ODP group. There was no difference in overall survival between the two groups (P=0.34). LDP is a safe and effective treatment for selected patients with pancreatic ductal adenocarcinoma. A slow-compression of pancreas tissue with the GIA stapler is effective in preventing postoperative pancreatic fistula. The oncologic outcome is comparable with the conventional open approach. Laparoscopic radical antegrade modular pancreatosplenectomy contributed to oncological clearance.

  4. Immunohistochemical Expression of Tissue Inhibitor of Metalloproteinase-1 (Timp-1 in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Suada Kuskunović

    2009-05-01

    Full Text Available Tissue inhibitor of metalloproteinase-1 (TIMP-1 is a natural inhibitor of matrix metalloproteinas-es (MMPs. Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immuno-histochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010. Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023. Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005. TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

  5. SMAD4 loss enables EGF, TGF?1 and S100A8/A9 induced activation of critical pathways to invasion in human pancreatic adenocarcinoma cells

    OpenAIRE

    Moz, Stefania; Basso, Daniela; Bozzato, Dania; Galozzi, Paola; Navaglia, Filippo; Negm, Ola H.; Arrigoni, Giorgio; Zambon, Carlo-Federico; Padoan, Andrea; Tighe, Paddy; Todd, Ian; Franchin, Cinzia; Pedrazzoli, Sergio; Punzi, Leonardo; Plebani, Mario

    2016-01-01

    Epidermal Growth Factor (EGF) receptor overexpression, KRAS, TP53, CDKN2A and SMAD4 mutations characterize pancreatic ductal adenocarcinoma. This mutational landscape might influence cancer cells response to EGF, Transforming Growth Factor ?1 (TGF?1) and stromal inflammatory calcium binding proteins S100A8/A9. We investigated whether chronic exposure to EGF modifies in a SMAD4-dependent manner pancreatic cancer cell signalling, proliferation and invasion in response to EGF, TGF?1 and S100A8/A...

  6. Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ.

    Science.gov (United States)

    Obeng-Gyasi, Samilia; Ong, Cecilia; Hwang, E Shelley

    2016-06-01

    The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.

  7. Anomalous pancreatic ductal system allowing distal bowel gas with duodenal atresia

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    Shruti Sevak

    2017-11-01

    Bypass of the atretic duodenal segment through an anomalous pancreatic ductal system is a rare anomaly described in the literature in only a handful of cases. This case report highlights the importance of considering duodenal atresia and pancreaticobiliary enteric bypass in the differential diagnosis of neonates presenting with partial duodenal obstruction. On ultrasound, the presence of gas in the biliary tree or pancreatic duct should alert the physician to the possibility of duodenal atresia with congenital pancreaticobiliary duct anomalies that allow for bypass of enteric contents, including air, into more distal bowel, thereby creating a gas pattern aptly described as double bubble with distal gas.

  8. FEATURES OF ISLET-LIKE CLUSTERS GENERATION IN PANCREATIC DUCTAL CELL MOLOLAYER CULTURING

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    L. A. Kirsanova

    2012-01-01

    Full Text Available Newborn rabbit pancreatic cell monolayer was obtained as we described earlier.The cultivated epithelial cells were shown by immunofluorescence to express special ductal marker CK19 and were insulin-and glucagon- negative for 10–15 days. A few fusiforms of nestin-positive cells were found in monolayer. Over 2 weeks in serum-free medium the plaques of epithelial cells became crowded and formed 3-dimentional structures – islet- like clusters. Islet-like clusters contain some insulin- and glucagon-positive cells recognized by immunohysto- chemistry staining. Pancreatic endocrine cell generation in 3-dimentional structures is discussed. 

  9. Aberrant Methylation of Preproenkephalin and p16 Genes in Pancreatic Intraepithelial Neoplasia and Pancreatic Ductal Adenocarcinoma

    OpenAIRE

    Fukushima, Noriyoshi; Sato, Norihiro; Ueki, Takashi; Rosty, Christophe; Walter, Kimberly M.; Wilentz, Robb E.; Yeo, Charles J.; Hruban, Ralph H.; Goggins, Michael

    2002-01-01

    Pancreatic intraductal neoplasia (PanIN) is thought to be the precursor to infiltrating pancreatic ductal adenocarcinoma. We have previously shown that the preproenkephalin (ppENK) and p16 genes are aberrantly methylated in pancreatic adenocarcinoma. In this study we define the methylation status of the ppENK and p16 genes in various grades of PanINs. One hundred seventy-four samples (28 nonneoplastic pancreatic epithelia, 7 reactive epithelia, 29 PanIN-1A, 48 PanIN-1B, 27 PanIN-2, 14 PanIN-3...

  10. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

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    Ingrid Paine

    2016-04-01

    Full Text Available Mathematics is often used to model biological systems. In mammary gland development, mathematical modeling has been limited to acinar and branching morphogenesis and breast cancer, without reference to normal duct formation. We present a model of ductal elongation that exploits the geometrically-constrained shape of the terminal end bud (TEB, the growing tip of the duct, and incorporates morphometrics, region-specific proliferation and apoptosis rates. Iterative model refinement and behavior analysis, compared with biological data, indicated that the traditional metric of nipple to the ductal front distance, or percent fat pad filled to evaluate ductal elongation rate can be misleading, as it disregards branching events that can reduce its magnitude. Further, model driven investigations of the fates of specific TEB cell types confirmed migration of cap cells into the body cell layer, but showed their subsequent preferential elimination by apoptosis, thus minimizing their contribution to the luminal lineage and the mature duct.

  11. Quantitatively characterizing the microstructural features of breast ductal carcinoma tissues in different progression stages by Mueller matrix microscope.

    Science.gov (United States)

    Dong, Yang; Qi, Ji; He, Honghui; He, Chao; Liu, Shaoxiong; Wu, Jian; Elson, Daniel S; Ma, Hui

    2017-08-01

    Polarization imaging has been recognized as a potentially powerful technique for probing the microstructural information and optical properties of complex biological specimens. Recently, we have reported a Mueller matrix microscope by adding the polarization state generator and analyzer (PSG and PSA) to a commercial transmission-light microscope, and applied it to differentiate human liver and cervical cancerous tissues with fibrosis. In this paper, we apply the Mueller matrix microscope for quantitative detection of human breast ductal carcinoma samples at different stages. The Mueller matrix polar decomposition and transformation parameters of the breast ductal tissues in different regions and at different stages are calculated and analyzed. For more quantitative comparisons, several widely-used image texture feature parameters are also calculated to characterize the difference in the polarimetric images. The experimental results indicate that the Mueller matrix microscope and the polarization parameters can facilitate the quantitative detection of breast ductal carcinoma tissues at different stages.

  12. Hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene.

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    Tiansuo Zhao

    Full Text Available CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α bound to the hypoxia-response element (HRE; 5'-A/GCGTG-3' of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC.

  13. Structural imaging of the pancreas in rat using micro-CT: application to a non-invasivelongitudinal evaluation of pancreatic ductal carcinoma monitoring

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    Akladios CY

    2013-04-01

    Full Text Available The aim of the study was to evaluate the feasibility of a longitudinal non-invasive monitoring of rat pancreatic ductal adenocarcinoma (PDAC using microCTscans (μCT. The identification of the pancreatic gland on (μCT was performed at first using contrast products (Fenestra LC and VC, v/v at a dosage of 0.5 ml/Kg of body weight. Then orthotopic PDAC developed in adult Lewis rat was detected and monitored. In vivo μCT measurement of tumor was compared to actual size ex vivo in 12 rats. Gemcitabine treatment of PDAC was monitored at two week intervals until defined endpoints (liver metastasis or ascitis in 10 rats versus 10 controls. μCT had a 100% positive predictive value in the detection of orthotropic PDAC. Regression analysis showed a linear correlation between ex vivo and in vivo μCT tumor measurements. Longitudinal evaluation of tumor progression showed a reduction in tumor growth (P<0.05 at 8 weeks and a slightly prolonged survival (P=0.15 under gemcitabine treatment. In conclusion μCT appears to be a cost-effective mean for preclinical study of PDAC saving time, animals, while respecting animal welfare. It could be considered as an efficient tool in anticancer drug research and development.

  14. Predictive values of BI-RADS{sup ®} magnetic resonance imaging (MRI) in the detection of breast ductal carcinoma in situ (DCIS)

    Energy Technology Data Exchange (ETDEWEB)

    Badan, Gustavo Machado, E-mail: gustavobadan@hotmail.com [Breast Imaging Service of Radiology Depatment—Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP (Brazil); Piato, Sebastião [Mastology Division—Gynecology and Obstetrics Department (Brazil); Roveda, Décio; Faria Castro Fleury, Eduardo de [Breast Imaging Service of Radiology Depatment—Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP (Brazil)

    2016-10-15

    Purpose: The purpose of this study was to evaluate BI-RADS indicators in the detection of DCIS by MRI. Materials and methods: Prospective observational study that started in 2014 and lasted 24 months. A total of 110 consecutive patients were evaluated, who presented with suspicious or highly suspicious microcalcifications on screening mammography (BI-RADS categories 4 and 5) and underwent stereotactic-guided breast biopsy, having had an MRI scan performed prior to biopsy. Results: Altogether, 38 cases were characterized as positive for malignancy, of which 25 were DCIS and 13 were invasive ductal carcinoma cases. MRI had a sensitivity of 96%; specificity of 75.67%; positive predictive value (PPV) for DCIS detection of 57.14%; negative predictive value (NPV) in the detection of DCIS of 98.24%; and an accuracy of 80.80%. Conclusion: BI-RADS as a tool for the detection of DCIS by MRI is a powerful instrument whose sensitivity was higher when compared to that observed for mammography in the literature. Likewise, the PPV obtained by MRI was higher than that observed in the present study for mammography, and the high NPV obtained on MRI scans can provide early evidence to discourage breast biopsy in selected cases.

  15. Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

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    Maria Kabbage

    2008-01-01

    Full Text Available Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF. The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, α-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues.

  16. Weight loss reduces breast ductal fluid estrogens in obese postmenopausal women: a single arm intervention pilot study

    Directory of Open Access Journals (Sweden)

    Carpenter Catherine L

    2012-12-01

    Full Text Available Abstract Background Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women. Methods We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2 postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass; exercise fitness (maximum oxygen consumption (VO2Max; 1-repetition strength maximum; and breast ductal lavage. Results Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop, VO2Max (+36% increase and strength improvement (+26%. Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline, estrone sulfate (−10%, estradiol (−25%, and Il-6 (−33%. Conclusions Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

  17. Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice.

    Science.gov (United States)

    He, Ping; Yang, Jong Won; Yang, Vincent W; Bialkowska, Agnieszka B

    2018-04-01

    Activating mutations in KRAS are detected in most pancreatic ductal adenocarcinomas (PDACs). Expression of an activated form of KRAS (KrasG12D) in pancreata of mice is sufficient to induce formation of pancreatic intraepithelial neoplasia (PanINs)-a precursor of PDAC. Pancreatitis increases formation of PanINs in mice that express KrasG12D by promoting acinar-to-ductal metaplasia (ADM). We investigated the role of the transcription factor Krüppel-like factor 5 (KLF5) in ADM and KRAS-mediated formation of PanINs. We performed studies in adult mice with conditional disruption of Klf5 (Klf5 fl/fl ) and/or expression of Kras G12D (LSL-Kras G12D ) via Cre ERTM recombinase regulated by an acinar cell-specific promoter (Ptf1a). Activation of Kras G12D and loss of KLF5 was achieved by administration of tamoxifen. Pancreatitis was induced in mice by administration of cerulein; pancreatic tissues were collected, analyzed by histology and immunohistochemistry, and transcriptomes were compared between mice that did or did not express KLF5. We performed immunohistochemical analyses of human tissue microarrays, comparing levels of KLF5 among 96 human samples of PDAC. UN-KC-6141 cells (pancreatic cancer cells derived from Pdx1-Cre;LSL-Kras G12D mice) were incubated with inhibitors of different kinases and analyzed in proliferation assays and by immunoblots. Expression of KLF5 was knocked down with small hairpin RNAs or CRISPR/Cas9 strategies; cells were analyzed in proliferation and gene expression assays, and compared with cells expressing control vectors. Cells were subcutaneously injected into flanks of syngeneic mice and tumor growth was assessed. Of the 96 PDAC samples analyzed, 73% were positive for KLF5 (defined as nuclear staining in more than 5% of tumor cells). Pancreata from Ptf1a-Cre ERTM ;LSL-Kras G12D mice contained ADM and PanIN lesions, which contained high levels of nuclear KLF5 within these structures. In contrast, Ptf1a-Cre ERTM ;LSL-Kras G12D ;Klf5 fl

  18. Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

    Directory of Open Access Journals (Sweden)

    Rute M.M. Ferreira

    2017-10-01

    Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

  19. A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

    Science.gov (United States)

    Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

    2016-04-01

    A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

  20. Preoperative diagnosis of ductal carcinoma in situ arising within a mammary fibroadenoma: a case report.

    Science.gov (United States)

    Ooe, Asako; Takahara, Sachiko; Sumiyoshi, Kazuhiro; Yamamoto, Hitoshi; Shiba, Eiichi; Kawai, Jun

    2011-07-01

    Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.

  1. Large palpable ductal carcinoma in situ is Her-2 positive with high nuclear grade.

    Science.gov (United States)

    Monabati, Ahmad; Sokouti, Ali-Reza; Noori, Sadat Noori; Safaei, Akbar; Talei, Abd-Rasul; Omidvari, Shapoor; Azarpira, Negar

    2015-01-01

    Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group with variable clinical presentation. The exact molecular mechanism is not known why some ductal carcinomas may reach to such a large size but still remains in situ. Although, molecular classification of DCIS lesions and nuclear grading are important for identification of more aggressive lesions but it is not sufficient. Our aim was to examine the expression pattern of immunohistochemical (IHC) markers of ER, PR, HER-2 in palpable DCIS lesions and compare with clinicopathological findings. Our center is referral hospital from South of Iran. Samples were obtained from fifty four patients with a diagnosis of palpable DCIS. Equivocal (2+) case in HER-2 IHC testing was more characterized by chromogenic in situ hybridization. The positive frequency of HER2, ER, and PR was 92%, 48%, and 37% respectively. Palpable DCIS lesions were significantly more HER-2 positive (92%). The DCIS cases were more likely to be of high nuclear grade (grade III) and Her-2 positive cases were more likely to be of high nuclear grade than intermediate grade. All ER negative tumors had high nuclear grade. The Her-2 positivity is suggested as the most important factor responsible for marked in situ proliferation and production of palpable mass.

  2. [A Case of Noninvasive Ductal Carcinoma of the Breast in a Male].

    Science.gov (United States)

    Yamashita, Yamato; Ishiba, Toshiyuki; Oda, Goshi; Nakagawa, Tsuyoshi; Aburatani, Tomoki; Ogo, Taiichi; Nakashima, Yutaka; Baba, Hironobu; Hoshino, Naoaki; Nishioka, Yoshinobu; Kawano, Tatsuyuki; Itoh, Takashi; Kirimura, Susumu; Kobayashi, Hirotoshi

    2017-11-01

    Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.

  3. PSC-derived Galectin-1 inducing epithelial-mesenchymal transition of pancreatic ductal adenocarcinoma cells by activating the NF-κB pathway

    Science.gov (United States)

    Tang, Dong; Zhang, Jingqiu; Yuan, Zhongxu; Zhang, Hongpeng; Chong, Yang; Huang, Yuqin; Wang, Jie; Xiong, Qingquan; Wang, Sen; Wu, Qi; Tian, Ying; Lu, Yongdie; Ge, Xiao; Shen, Wenjing; Wang, Daorong

    2017-01-01

    Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues. In addition, our in vitro studies showed PSC-derived Galectin-1 promoted the proliferation, invasion, and survival (anti-apoptotic effects) of PANC-1 cells. We also showed PSC-derived Galectin-1 induced EMT of PANC-1 cells and activated the NF-кB pathway in vitro. Our mixed (PSCs and PANC-1 cells) mouse orthotopic xenograft model indicated that overexpression of Galectin-1 in PSCs significantly promoted the proliferation, growth, invasion, and liver metastasis of the transplanted tumor. Moreover, Galectin-1 overexpression in PSCs was strongly associated with increased expression of EMT markers in both the orthotopic xenograft tumor in the pancreas and in metastatic lesions of naked mice. We conclude that PSC-derived Galectin-1 promotes the malignant behavior of PDAC by inducing EMT via activation of the NF-κB pathway. Our results suggest that targeting Galectin-1 in PSCs could represent a promising therapeutic strategy for PDAC progression and metastasis. PMID:29156810

  4. Immune Infiltration in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Desmedt, Christine; Salgado, Roberto; Fornili, Marco; Pruneri, Giancarlo; Van den Eynden, Gert; Zoppoli, Gabriele; Rothé, Françoise; Buisseret, Laurence; Garaud, Soizic; Willard-Gallo, Karen; Brown, David; Bareche, Yacine; Rouas, Ghizlane; Galant, Christine; Bertucci, François; Loi, Sherene; Viale, Giuseppe; Di Leo, Angelo; Green, Andrew R; Ellis, Ian O; Rakha, Emad A; Larsimont, Denis; Biganzoli, Elia; Sotiriou, Christos

    2018-02-20

    Invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal cancer (IDC). Here, we aimed at evaluating the prevalence, levels, and composition of tumor-infiltrating lymphocytes (TILs) and their association with clinico-pathological and outcome variables in ILC, and to compare them with IDC. We considered two patient series with TIL data: a multicentric retrospective series (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n = 468) patients from the Nottingham series, as well as the CIBERSORT immune profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All statistical tests were two-sided. TIL levels were statistically significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence interval = 0.70 to 0.88, P lobular series, although they did not reach statistical significance in the latter. The Nottingham series revealed that the levels of intratumoral but not total CD8+ were statistically significantly lower in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted statistically significant differences in terms of immune composition. This study shows differences between the immune infiltrates of ER-positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization, composition, and clinical associations.

  5. Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+ tumor infiltrating lymphocytes in ductal and lobular breast cancers

    International Nuclear Information System (INIS)

    Droeser, Raoul; Zlobec, Inti; Kilic, Ergin; Güth, Uwe; Heberer, Michael; Spagnoli, Giulio; Oertli, Daniel; Tapia, Coya

    2012-01-01

    Clinical relevance of tumor infiltrating lymphocytes (TILs) in breast cancer is controversial. Here, we used a tumor microarray including a large series of ductal and lobular breast cancers with long term follow up data, to analyze clinical impact of TIL expressing specific phenotypes and distribution of TILs within different tumor compartments and in different histological subtypes. A tissue microarray (TMA) including 894 ductal and 164 lobular breast cancers was stained with antibodies recognizing CD4, FOXP3, and IL-17 by standard immunohistochemical techniques. Lymphocyte counts were correlated with clinico-pathological parameters and survival. CD4 + lymphocytes were more prevalent than FOXP3 + TILs whereas IL-17 + TILs were rare. Increased numbers of total CD4 + and FOXP3 + TIL were observed in ductal, as compared with lobular carcinomas. High grade (G3) and estrogen receptor (ER) negative ductal carcinomas displayed significantly (p < 0.001) higher CD4 + and FOXP3 + lymphocyte infiltration while her2/neu over-expression in ductal carcinomas was significantly (p < 0.001) associated with higher FOXP3 + TIL counts. In contrast, lymphocyte infiltration was not linked to any clinico-pathological parameters in lobular cancers. In univariate but not in multivariate analysis CD4 + infiltration was associated with significantly shorter survival in patients bearing ductal, but not lobular cancers. However, a FOXP3 + /CD4 + ratio > 1 was associated with improved overall survival even in multivariate analysis (p = 0.033). Ductal and lobular breast cancers appear to be infiltrated by different lymphocyte subpopulations. In ductal cancers increased CD4 + and FOXP3 + TIL numbers are associated with more aggressive tumor features. In survival analysis, absolute numbers of TILs do not represent major prognostic indicators in ductal and lobular breast cancer. Remarkably however, a ratio > 1 of total FOXP3 + /CD4 + TILs in ductal carcinoma appears to represent an independent

  6. [Bushen Huoxue Fang promotes the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia].

    Science.gov (United States)

    Sun, Jie; Li, Qiu-Fen; Tian, Dai-Zhi; Jiang, Shao-Bo; Wu, Xian-De; Qiu, Shun-An; Ren, Xiao-Gang; Li, Yu-Bing

    2014-09-01

    To investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism. One hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay. The expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.

  7. Local Recurrences After Conservative Treatment of Ductal Carcinoma-In-Situ of the Breast Without Radiotherapy: The Effect of Age

    NARCIS (Netherlands)

    Schouten van der Velden, A.P.; Peeters, P.H.M.; Koot, V.C.M.; Hennipman, A.

    2006-01-01

    Background: The main goal in treatment of ductal carcinoma-in-situ (DCIS) of the breast is to prevent local recurrences. Radiotherapy after breast-conserving surgery has been shown to decrease the recurrence rate, although whether all patients should be treated with radiotherapy remains a topic

  8. Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes

    Science.gov (United States)

    Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D.; Zeng, Defu

    2016-01-01

    We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9+ (Sox9+) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9+ ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9+ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300–450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9+ ductal cell differentiation into β cells in adult mice. PMID:26733677

  9. Ansa Pancreatica: A Case Report of a Type of Ductal Variation in a Patient with Idiopathic Acute Recurrent Pancreatitis

    International Nuclear Information System (INIS)

    Kim, Hye Mi; Park, Jung Yup; Kim, Myeong Jin

    2010-01-01

    Ansa pancreatica is a rare type of pancreatic ductal variation. Recently, ansa pancreatic has been considered as a predisposing factor in patients with idiopathic acute pancreatitis. To the best of our knowledge, no previously published report in Korea has described ansa pancreatica. We report a case of acute recurrent pancreatitis with ansa pancreatica, which was revealed on magnetic resonance cholangiopancreatography (MRCP)

  10. Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS)

    NARCIS (Netherlands)

    Hartwig, Werner; Vollmer, Charles M.; Fingerhut, Abe; Yeo, Charles J.; Neoptolemos, John P.; Adham, Mustapha; Andrén-Sandberg, Ake; Asbun, Horacio J.; Bassi, Claudio; Bockhorn, Max; Charnley, Richard; Conlon, Kevin C.; Dervenis, Christos; Fernandez-Cruz, Laureano; Friess, Helmut; Gouma, Dirk J.; Imrie, Clem W.; Lillemoe, Keith D.; Milićević, Miroslav N.; Montorsi, Marco; Shrikhande, Shailesh V.; Vashist, Yogesh K.; Izbicki, Jakob R.; Büchler, Markus W.

    2014-01-01

    Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to

  11. Diet-induced inflammation and mammary ductal development: Alternative activation of estrogen-dependent stromal-epithelial signaling

    Science.gov (United States)

    The mechanisms controlling allometric development of the mammary ductal tree have largely been defined through key studies in rodent model systems. The development of this system is known to depend on the integrated actions of pituitary and ovarian hormones, locally produced growth factors, extracel...

  12. “Stealth dissemination” of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Circulating tumor cells (CTCs) appear to be involved in early dissemination of many cancers, although which characteristics are important in metastatic spread are not clear. Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal a...

  13. Repeatability and correlations of dynamic contrast enhanced and T2* MRI in patients with advanced pancreatic ductal adenocarcinoma

    NARCIS (Netherlands)

    Klaassen, Remy; Gurney-Champion, Oliver J.; Wilmink, Johanna W.; Besselink, Marc G.; Engelbrecht, Marc R. W.; Stoker, Jaap; Nederveen, Aart J.; van Laarhoven, Hanneke W. M.

    2018-01-01

    In current oncological practice of pancreatic ductal adenocarcinoma (PDAC), there is a great demand for response predictors and markers for early treatment evaluation. In this study, we investigated the repeatability and the interaction of dynamic contrast enhanced (DCE) and T2* MRI in patients with

  14. Continuous indomethacin infusion may be less effective than bolus infusions for ductal closure in very low birth weight infants

    NARCIS (Netherlands)

    de Vries, NKS; Jagroep, FK; Jaarsma, AS; Elzenga, NJ; Bos, AF

    The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates

  15. PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Saukkonen, Kapo; Hagström, Jaana; Mustonen, Harri; Juuti, Anne; Nordling, Stig; Kallio, Pauliina; Alitalo, Kari; Seppänen, Hanna; Haglund, Caj

    2016-01-01

    The Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of β-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/β-catenin signaling and it is involved in carcinogenesis through alterations in its expression. The actions can be either oncogenic or tumor suppressive depending on the tissue. The aim of this study was to investigate PROX1 and β-catenin expression in pancreatic ductal adenocarcinoma (PDAC). Expression of PROX1 and β-catenin were evaluated in 156 patients by immunohistochemistry of tissue microarrays. Associations between tumor marker expression and clinicopathological parameters were assessed by the Fischer’s exact-test or the linear-by-linear association test. The Kaplan-Meier method and log-rank test were used for survival analysis. Uni- and multivariate survival analyses were carried out by the Cox regression proportional hazard model. High PROX1 expression was seen in 74 (48 %) tumors, and high β-catenin expression in 100 (65 %). High β-catenin expression was associated with lower tumor grade (p = 0.025). High PROX1 and β-catenin expression associated significantly with lower risk of death from PDAC in multivariate analysis (HR = 0.63; 95 % CI 0.42–0.95, p = 0.026; and HR = 0.54; 95 % CI 0.35–0.82, p = 0.004; respectively). The combined high expression of PROX1 and β-catenin also predicted lower risk of death from PDAC (HR = 0.46; 95 % CI 0.28–0.76, p = 0.002). In conclusion, high PROX1 and β-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma. The online version of this article (doi:10.1186/s12885-016-2497-5) contains supplementary material, which is available to authorized users

  16. Secretion of N-ERC/mesothelin and expression of C-ERC/mesothelin in human pancreatic ductal carcinoma.

    Science.gov (United States)

    Inami, Koichi; Kajino, Kazunori; Abe, Masaaki; Hagiwara, Yoshiaki; Maeda, Masahiro; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

    2008-12-01

    ERC/mesothelin gene (MSLN) encodes a precursor protein, which is cleaved by proteases to generate N-ERC/mesothelin and C-ERC/mesothelin. N-ERC/mesothelin is a soluble protein, also known as megakaryocyte-potentiating factor, which is released into extracellular space. N-ERC/mesothelin is known to be a serum marker of mesothelioma. We have previously developed an enzyme-linked immunosorbent assay system for N-ERC/mesothelin, which can detect mesothelioma. C-ERC/mesothelin is expressed in normal mesothelial cell, pancreatic cancers, ovarian cancers, mesotheliomas and some other cancers. Pancreatic ductal carcinoma remains a fatal disease because its diagnosis often occurs very late. In this study, we examined ERC/mesothelin expression in human pancreatic cancer cell lines (MIA-PaCa2, PK-1, KP-3, TCC-PAN2, PK-59 and PK-45H) by reverse transcription-polymerase chain reaction and immunoblotting and N-ERC/mesothelin concentration in the supernatant of cultured cancer cells by the ELISA system. We also investigated C-ERC/mesothlein expression in human pancreatic ductal carcinoma tissues by immunostaining using 5B2 anti-mesothelin monoclonal antibody and N-ERC/mesothelin concentration in sera obtained from patients with pancreatic ductal carcinoma via ELISA. In vitro, N-ERC/mesothelin concentration in cell culture medium nearly correlated with the expression level of C-ERC/mesothelin. Although C-ERC/mesothelin was frequently expressed in human pancreatic ductal carcinoma, serum N-ERC/mesothelin concentration of cancer patients was equivalent to healthy controls. N-ERC/mesothelin was not useful as a serum marker of pancreatic ductal carcinoma, but because of frequent expression, C-ERC/mesothelin might be useful as a target of molecular imaging and immunotherapy.

  17. Persistence of Coxsackievirus B4 in pancreatic ductal-like cells results in cellular and viral changes.

    Science.gov (United States)

    Alidjinou, E K; Engelmann, I; Bossu, J; Villenet, C; Figeac, M; Romond, M-B; Sané, F; Hober, D

    2017-10-03

    Although known as cytolytic viruses, group B coxackieviruses (CVB) are able to establish a persistent infection in vitro and in vivo. Viral persistence has been reported as a key mechanism in the pathogenesis of CVB-associated chronic diseases such as type 1 diabetes (T1D). The impact of CVB4 persistence on human pancreas ductal-like cells was investigated. A persistent CVB4 infection was established in ductal-like cells. PDX-1 expression, resistance to CVB4-induced lysis and CAR expression were evaluated. The profile of cellular microRNAs (miRNAs) was investigated through miRNA-sequencing. Viral phenotypic changes were examined, and genomic modifications were assessed by sequencing of the viral genome. The CVB4 persistence in ductal-like cells was productive, with continuous release of infectious particles. Persistently infected cells displayed a resistance to CVB4-induced lysis upon superinfection and expression of PDX-1 and CAR was decreased. These changes were maintained even after virus clearance. The patterns of cellular miRNA expression in mock-infected and in CVB4-persistently infected ductal-like cells were clearly different. The persistent infection-derived virus (PIDV) was still able to induce cytopathic effect but its plaques were smaller than the parental virus. Several mutations appeared in various PIDV genome regions, but amino acid substitutions did not affect the predicted site of interaction with CAR. Cellular and viral changes occur during persistent infection of human pancreas ductal-like cells with CVB4. The persistence of cellular changes even after virus clearance supports the hypothesis of a long-lasting impact of persistent CVB infection on the cells.

  18. A simple ductal mammary papilloma in a male maned wolf (Chrysocyon brachyurus).

    Science.gov (United States)

    Cassali, Geovanni D; Bertagnolli, Angélica C; Ferreira, Enio; Malta, Marcelo C C

    2009-01-01

    A 1-cm-diameter nodule was identified in the left inguinal mammary gland of a 9-year-old male maned wolf (Chrysocyon brachyurus). The mass was surgically excised and examined histologically. Microscopically, the neoplasm consisted of papillary proliferations of epithelial cells on well-defined fibrovascular stalks. A myoepithelial layer was located between the single layer of epithelial cells and the fibrovascular stalk. This histologic appearance was compatible with a diagnosis of simple ductal mammary papilloma. Immunohistochemical staining was positive for p63, cytokeratins AE1/AE3, and estrogen receptors. The clinical and histologic observations in the present case indicate that male maned wolves may develop mammary tumors that are similar to those observed in domestic dogs and humans.

  19. Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status.

    Science.gov (United States)

    Silverstein, Melvin J; Buchanan, Claire

    2003-12-01

    As our knowledge of ductal carcinoma in situ (DCIS) continues to evolve, treatment decision-making has become increasingly complex and controversial for both patients and physicians. Treatment options include mastectomy, and breast conservation with or without radiation therapy. Data produced from the randomized clinical trials for DCIS has provided the basis for important treatment recommendations, but are not without limitations. In this article, we review our prospectively collected database consisting of 1036 patients with DCIS treated at the Van Nuys Breast Center and the USC/Norris Comprehensive Cancer Center. We review the use of the USC/Van Nuys Prognostic Index, a clinical algorithm designed to assist physicians in selection of appropriate treatments, and examine the impact of margin status as a sole predictor of local recurrence.

  20. The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology.

    Science.gov (United States)

    Hegyi, Peter; Petersen, Ole H

    2013-01-01

    There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other.

  1. Extension of ductal carcinoma in situ. Histopathological association with MR imaging and mammography

    International Nuclear Information System (INIS)

    Shiraishi, Akihiko; Kurosaki, Yoshihisa; Maehara, Tadayuki

    2003-01-01

    The purpose of this study is to evaluate the capability of breast MRI (magnetic resonance imaging) and mammography in determining tumor extent and the detectability of ductal carcinoma in situ (DCIS) in association with histopathological features. Thirty women with breast cancer underwent 3D dynamic MRI. Twelve women had pure DCIS and 18 women had DCIS with microinvasion. We analyzed the results of preoperative MRI and mammography with histopathologic results, retrospectively. The mean lesion size was 55.1 mm from the histopathologic results. Twenty-six lesions were detected through the MRI (a sensitivity of 86.7%). MRI depicted eight lesions without mammographically detected microcalcification. In seven cases, MRI showed tumor extent accurately compared with mammography, and the combined diagnosis improved the accuracy of evaluating tumor extent. MRI can complement mammography in guiding surgical treatment of DCIS by providing better assessment of the extent of the lesion. (author)

  2. Ductal Carcinoma In Situ: What Can We Learn from Clinical Trials?

    Directory of Open Access Journals (Sweden)

    Lucio Fortunato

    2012-01-01

    Full Text Available Ductal Carcinoma in situ has been diagnosed more frequently in the last few years and now accounts for approximately one-fourth of all treated breast cancers. Traditionally, this disease has been treated with total mastectomy, but conservative surgery has become increasingly used in the absence of unfavourable clinical conditions, if a negative excision margin can be achieved. It is controversial whether subgroups of patients with favourable in situ tumors could be managed by conservative surgery alone, without radiation. As the disease is diagnosed more frequently in younger patients, these issues are very relevant, and much research has focused on this topic in the last two decades. We reviewed randomized trials regarding adjuvant radiation after breast-conservative surgery and compared data with available retrospective studies.

  3. Immunohistochemical evaluation of vasopressin expression in breast fibrocystic disease and ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    North, William G; Wells, Wendy; Fay, Michael J; Mathew, Rennie S; Donnelly, Edward M; Memoli, Vincent A

    2003-01-01

    We previously found that expression of the vasopressin gene is a common feature of human breast cancer. In the present study we first examined 21 different cases of benign fibrocystic breast disease for vasopressin expression using immunohistochemistry and antibodies directed against vasopressin (anti-VP) and against vasopressin-associated glycopeptide (anti-VAG). All cases examined were negative for vasopressin gene expression using these antibodies. Alternatively, we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second of these antibodies (anti-VAG), and all of these cases were positive for vasopressin gene expression. Our results suggest that products of vasopressin gene expression are not markers of cellular proliferation in the breast, and might rather represent an early part of the carcinogenic process in this tissue.

  4. Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression

    DEFF Research Database (Denmark)

    Laklai, Hanane; Miroshnikova, Yekaterina A.; Pickup, Michael W.

    2016-01-01

    by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were......Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop...... stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression...

  5. The use of sentinel lymph node biopsy in the treatment of breast ductal carcinoma in situ

    DEFF Research Database (Denmark)

    Holm-Rasmussen, Emil Villiam; Jensen, Maj Britt; Balslev, Eva

    2017-01-01

    . In the present study, the use of SLNB in patients with DCIS was evaluated nationally and compared across Danish departments. Material and methods A register-based study was conducted using the Danish Breast Cancer Group database. The use of SLNB in DCIS patients according to year of diagnosis, age at diagnosis......, size of lesion, Van Nuys classification, palpability, location and department of surgery was evaluated. The chi-squared test was used to test differences between the groups. Results Data from 2618 Danish female patients diagnosed with DCIS between 2004 and 2015 were included; 54.3% of patients......Objectives The risk of axillary metastases in breast cancer patients with only ductal carcinoma in situ (DCIS) is low. Thus, axillary staging with sentinel lymph node biopsy (SLNB) should only be used according to the current guidelines to avoid over-treatment and unnecessary morbidity...

  6. CI- and K+ Channels in Pancreatic Ductal Adenocarcinoma (PDAC)

    DEFF Research Database (Denmark)

    Sauter, Daniel Rafael Peter

    moderate survival benefits. Therefore, novel targets are urgently needed. Cl- and K+ channels play integral roles in the regulation of critical cellular processes such as proliferation, apoptosis and migration. These processes are commonly perturbed in tumor cells. A phenotypic hallmark of cancer is its......Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers with >95% of the affected dying from it. Despite of intensive efforts to develop new therapeutic strategies, only few drugs (e.g. gemcitabine, erlotinib) are currently approved for treatment, all exhibit only...... pancreatic cancer cell lines (Capan-1, BxPC-3 and AsPC-1) revealed Ca2+-activated Cl- current that showed the biophysical signature of ANO1 (TMEM16A). In line with this, application of ANO1-specific inhibitors and transient gene silencing of ANO1 abrogated this current. Using scratch wound healing assay, we...

  7. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  8. Development of a miRNA-based diagnostic assay for pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Szafranska-Schwarzbach, Anna E; Adai, Alex T; Lee, Linda S; Conwell, Darwin L; Andruss, Bernard F

    2011-04-01

    Diagnosis of pancreatic cancer remains a clinical challenge. Both chronic pancreatitis and pancreatic cancer may present with similar symptoms and similar imaging features, often leading to incorrect interpretation. Thus, the use of an objective molecular test that can discriminate between chronic pancreatitis and pancreatic cancer will be a valuable asset in obtaining a definitive diagnosis of pancreatic cancer. Following Clinical Laboratory Improvement Amendments and College of American Pathologists guidelines, Asuragen Clinical Services Laboratory has developed and validated a laboratory-developed test, miRInform(®) Pancreas, to aid in the identification of pancreatic ductal adenocarcinoma. This molecular diagnostic tool uses reverse-transcription quantitative PCR to measure the expression difference between two miRNAs, miR-196a and miR-217, in fixed tissue specimens. This article describes the test validation process as well as determination of performance parameters of miRInform Pancreas.

  9. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

    Science.gov (United States)

    Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina

    2015-11-02

    The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

  10. An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Felts, Jesse L; Zhu, Junjia; Han, Bing; Smith, Stanley J; Truica, Cristina I

    2017-11-01

    The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone-positive, Her-2-negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow-up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost-effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated. © 2017 Wiley Periodicals, Inc.

  11. Sirtuin-1 regulates acinar-to-ductal metaplasia and supports cancer cell viability in pancreatic cancer.

    Science.gov (United States)

    Wauters, Elke; Sanchez-Arévalo Lobo, Victor J; Pinho, Andreia V; Mawson, Amanda; Herranz, Daniel; Wu, Jianmin; Cowley, Mark J; Colvin, Emily K; Njicop, Erna Ngwayi; Sutherland, Rob L; Liu, Tao; Serrano, Manuel; Bouwens, Luc; Real, Francisco X; Biankin, Andrew V; Rooman, Ilse

    2013-04-01

    The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD(+)-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1 activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and β-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6. In PDAC, acetylation of β-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis. ©2012 AACR.

  12. Ductal carcinoma of breast: nuclear grade as a predictor of S-phase fraction.

    Science.gov (United States)

    Dabbs, D J

    1993-06-01

    Nuclear grade (NG) and S-phase fraction (SPF) are established independent prognostic variables for ductal breast carcinomas. Nuclear grade can be assigned by a pathologist in a simple fashion during histopathologic evaluation of the tumor, while SPF requires flow cytometric evaluation of tumor samples. This prospective study was undertaken to determine whether elevated SPF could be predicted from NG alone and how NG and SPF correlate with c-erbB-2 expression. Eighty-two breast carcinomas of ductal type were assigned an NG of low (grade 1 or grade 2) or high (grade 3). S-phase fraction was recorded initially from fresh-frozen tissue samples and was designated as either low SPF (below the value designated as the cutoff for elevated SPF) or high SPF (a value at or greater than the cutoff value). On fresh tissue the NG predicted the range of SPF (low or high) in 89% of cases. Four percent of the cases that did not correlate could definitely be attributed to sample error. The remaining 7% that did not correlate could have been due to sample error, specimen quality, or tumor heterogeneity, as demonstrated by reversal of SPF range as performed on paraffin blocks of tumor. Eighty-eight percent of the tumors positive for c-erbB-2 were NG 3 and 12% were NG 2. All c-erbB-2 tumors were aneuploid. This study demonstrates the importance of carefully assigning NGs on tissue and indicates the importance of reviewing flow cytometric data side by side with histopathologic parameters to detect discrepancies between these two modalities. Careful nuclear grading assignment can accurately predict the range of SPF.

  13. Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Janky, Rekin’s; Binda, Maria Mercedes; Allemeersch, Joke; Van den broeck, Anke; Govaere, Olivier; Swinnen, Johannes V.; Roskams, Tania; Aerts, Stein; Topal, Baki

    2016-01-01

    Pancreatic cancer is poorly characterized at genetic and non-genetic levels. The current study evaluates in a large cohort of patients the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC). We performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 histologically normal pancreatic tissue samples. Cox regression models were used to study the effect on survival of molecular subtypes and 16 clinicopathological prognostic factors. In order to better understand the biology of PDAC we used iRegulon to identify transcription factors (TFs) as master regulators of PDAC and its subtypes. We confirmed the PDAssign gene signature as classifier of PDAC in molecular subtypes with prognostic relevance. We found molecular subtypes, but not clinicopathological factors, as independent predictors of survival. Regulatory network analysis predicted that HNF1A/B are among thousand TFs the top enriched master regulators of the genes expressed in the normal pancreatic tissue compared to the PDAC regulatory network. On immunohistochemistry staining of PDAC samples, we observed low expression of HNF1B in well differentiated towards no expression in poorly differentiated PDAC samples. We predicted IRF/STAT, AP-1, and ETS-family members as key transcription factors in gene signatures downstream of mutated KRAS. PDAC can be classified in molecular subtypes that independently predict survival. HNF1A/B seem to be good candidates as master regulators of pancreatic differentiation, which at the protein level loses its expression in malignant ductal cells of the pancreas, suggesting its putative role as tumor suppressor in pancreatic cancer. The study was registered at ClinicalTrials.gov under the number NCT01116791 (May 3, 2010). The online version of this article (doi:10.1186/s12885-016-2540-6) contains supplementary material, which is available to authorized users

  14. Biostatistical analysis of treatment results of bacterial liver abscesses using minimally invasive techniques and open surgery

    Directory of Open Access Journals (Sweden)

    Кipshidze A.A.

    2013-12-01

    Full Text Available Today bacterial abscesses remain one of the most difficult complications in surgical hepatology, both traditional and minimally invasive methods of their treatment are used. Bio-statistical analysis is used due to the fact that strong evidences are required for the effectiveness of one or another method of surgical intervention. The estimation of statistical significance of differences between the control and the main group of patients with liver abscesses is given in this paper. Depending on the treatment method patients were divided into two groups: 1 - minimally invasive surgery (89 cases; 2 – laporatomy surgery (74 patients. Data compa¬ri¬son was performed by means of Stjudent's criterion. The effectiveness of method of abscesses drainage using inter¬ventional sonography, outer nazobiliar drainage with reorganization of ductal liver system and abscess cavity with the help of modern antiseptics was considered. The percentage of cured patients was also estimated.

  15. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast...... cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly......(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P

  16. Deeply invasive candidiasis.

    NARCIS (Netherlands)

    Ostrosky-Zeichner, L.; Rex, J.H.; Bennett, J.; Kullberg, B.J.

    2002-01-01

    The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology. Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease.

  17. Cryptic invasions: a review

    Czech Academy of Sciences Publication Activity Database

    Morais, Pedro Miguel; Reichard, Martin

    613-614, February (2018), s. 1438-1448 ISSN 0048-9697 R&D Projects: GA ČR GA13-05872S Institutional support: RVO:68081766 Keywords : Conspecific invader * Biological invasions * Bibliometric * Invasiveness Subject RIV: EG - Zoology OBOR OECD: Environmental sciences (social aspects to be 5.7) Impact factor: 4.900, year: 2016

  18. Factors influencing plant invasiveness

    Science.gov (United States)

    Yvette Ortega; Dean Pearson

    2009-01-01

    Invasiveness of spotted knapweed and biological control agents. Dean and Yvette are examining the influence of drought on the invasiveness of spotted knapweed (Centaurea maculosa) and its susceptibility to herbivory by biological control agents. In collaboration with the University of Montana and Forest Health Protection, researchers have constructed 150...

  19. Alien invasive birds.

    Science.gov (United States)

    Brochier, B; Vangeluwe, D; van den Berg, T

    2010-08-01

    A bird species is regarded as alien invasive if it has been introduced, intentionally or accidentally, to a location where it did not previously occur naturally, becomes capable of establishing a breeding population without further intervention by humans, spreads and becomes a pest affecting the environment, the local biodiversity, the economy and/or society, including human health. European Starling (Sturnus vulgaris), Common Myna (Acridotheres tristis) and Red-vented Bulbul (Pycnonotus cafer) have been included on the list of '100 of the World's Worst Invasive Alien Species', a subset of the Global Invasive Species Database. The 'Delivering Alien Invasive Species Inventories for Europe' project has selected Canada Goose (Branta canadensis), Ruddy Duck (Oxyura jamaicensis), Rose-ringed Parakeet (Psittacula krameri) and Sacred Ibis (Threskiornis aethiopicus) as among 100 of the worst invasive species in Europe. For each of these alien bird species, the geographic range (native and introduced range), the introduction pathway, the general impacts and the management methods are presented.

  20. Minimally invasive orthognathic surgery.

    Science.gov (United States)

    Resnick, Cory M; Kaban, Leonard B; Troulis, Maria J

    2009-02-01

    Minimally invasive surgery is defined as the discipline in which operative procedures are performed in novel ways to diminish the sequelae of standard surgical dissections. The goals of minimally invasive surgery are to reduce tissue trauma and to minimize bleeding, edema, and injury, thereby improving the rate and quality of healing. In orthognathic surgery, there are two minimally invasive techniques that can be used separately or in combination: (1) endoscopic exposure and (2) distraction osteogenesis. This article describes the historical developments of the fields of orthognathic surgery and minimally invasive surgery, as well as the integration of the two disciplines. Indications, techniques, and the most current outcome data for specific minimally invasive orthognathic surgical procedures are presented.

  1. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

  2. Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.

    Science.gov (United States)

    Raap, Mieke; Gronewold, Malte; Christgen, Henriette; Glage, Silke; Bentires-Alj, Mohammad; Koren, Shany; Derksen, Patrick W; Boelens, Mirjam; Jonkers, Jos; Lehmann, Ulrich; Feuerhake, Friedrich; Kuehnle, Elna; Gluz, Oleg; Kates, Ronald; Nitz, Ulrike; Harbeck, Nadia; Kreipe, Hans H; Christgen, Matthias

    2018-01-01

    Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (Pinvasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (Plobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

  3. HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer

    Science.gov (United States)

    Roses, Robert E.; Paulson, E. Carter; Sharma, Anupama; Schueller, Jeanne E.; Nisenbaum, Harvey; Weinstein, Susan; Fox, Kevin R.; Zhang, Paul J.; Czerniecki, Brian J.

    2009-01-01

    The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a multivariate logistic regression were done to determine whether estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis, nuclear grade, lesion size, or patient age predicted the presence of associated invasive disease in patients with DCIS. Invasive foci were found in association with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not overexpress HER2. Although high nuclear grade, large lesion size, and HER2 overexpression were all associated with the presence of invasive disease on univariate analysis, HER2 was the only significant predictor for the presence of invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These data indicate that HER2 overexpression in DCIS lesions predicts the presence of invasive foci in patients with DCIS and suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression. PMID:19383888

  4. Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

    Science.gov (United States)

    Toyoshima, Masafumi; Iwahashi, Hideki; Shima, Takashi; Hayasaka, Atsushi; Kudo, Takako; Makino, Hiromitsu; Igeta, Saori; Matsuura, Rui; Ishigaki, Nobuko; Akagi, Kozo; Sakurada, Junko; Suzuki, Hiroyoshi; Yoshinaga, Kosuke

    2015-02-14

    Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

  5. Lobular breast cancers lack the inverse relationship between ER/PR status and cell growth rate characteristic of ductal cancers in two independent patient cohorts: implications for tumor biology and adjuvant therapy.

    Science.gov (United States)

    Wong, Hilda; Lau, Silvia; Cheung, Polly; Wong, Ting Ting; Parker, Andrew; Yau, Thomas; Epstein, Richard J

    2014-11-10

    Although invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma (IDC) in numerous respects - including its genetics, clinical phenotype, metastatic pattern, and chemosensitivity - most experts continue to manage ILC and IDC identically in the adjuvant setting. Here we address this discrepancy by comparing early-stage ILC and IDC in two breast cancer patient cohorts of differing nationality and ethnicity. The clinicopathologic features of 2029 consecutive breast cancer patients diagnosed in Hong Kong (HK) and Australia (AUS) were compared. Interrelationships between tumor histology and other clinicopathologic variables, including ER/PR and Ki67, were analysed. Two hundred thirty-nine patients were identified with ILC (11.8%) and 1790 patients with IDC. AUS patients were older (p patients. As expected, ILC tumors were lower in grade and proliferative rate, and more often ER-positive and HER2-negative, than IDC (p 0.7). Moreover, whereas IDC tumors exhibited a strongly negative relationship between ER/PR and Ki67 status (p 0.6). These data imply that the primary adhesion defect in ILC underlies a secondary stromal-epithelial disconnect between hormonal signaling and tumor growth, suggesting in turn that this peritumoral feedback defect could reduce both the antimetastatic (adjuvant) and tumorilytic (palliative) efficacy of cytotoxic therapies for such tumors. Hence, we caution against assuming similar adjuvant chemotherapeutic survival benefits for ILC and IDC tumors with similar ER and Ki67, whether based on immunohistochemical or gene expression assays.

  6. Transcriptomic and genomic features of invasive lobular breast cancer.

    Science.gov (United States)

    Desmedt, Christine; Zoppoli, Gabriele; Sotiriou, Christos; Salgado, Roberto

    2017-06-01

    Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Benoit, Vivian; Laenkholm, Anne-Vibeke

    2006-01-01

    to both immunological and endogenous cellular factors, although little is known about the distinct biology of MCB that may contribute to the improved outcome of MCB patients. To identify candidate genes, we performed gene array expression analysis of cell lines of MCB, ductal breast cancer and normal......Medullary breast cancer (MCB) is a morphologically and biologically distinct subtype that, despite cytologically highly malignant characteristics, has a favorable prognosis compared to the more common infiltrating ductal breast carcinoma. MCB metastasizes less frequently, which has been attributed...... breast epithelia, and the differential expression of a panel of candidate genes was further validated by quantitative PCR and immunohistochemical analysis of cell lines and tumor biopsies. A limited number of genes, including several members of the GAGE and insulin growth factor binding protein (IGFBP...

  9. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

    OpenAIRE

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2011-01-01

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends o...

  10. Comparison of self-expandable and balloon-expanding stents for hybrid ductal stenting in hypoplastic left heart complex.

    Science.gov (United States)

    Goreczny, Sebastian; Qureshi, Shakeel A; Rosenthal, Eric; Krasemann, Thomas; Nassar, Mohamed S; Anderson, David R; Morgan, Gareth J

    2017-07-01

    We aimed to compare the procedural and mid-term performance of a specifically designed self-expanding stent with balloon-expandable stents in patients undergoing hybrid palliation for hypoplastic left heart syndrome and its variants. The lack of specifically designed stents has led to off-label use of coronary, biliary, or peripheral stents in the neonatal ductus arteriosus. Recently, a self-expanding stent, specifically designed for use in hypoplastic left heart syndrome, has become available. We carried out a retrospective cohort comparison of 69 neonates who underwent hybrid ductal stenting with balloon-expandable and self-expanding stents from December, 2005 to July, 2014. In total, 43 balloon-expandable stents were implanted in 41 neonates and more recently 47 self-expanding stents in 28 neonates. In the balloon-expandable stents group, stent-related complications occurred in nine patients (22%), compared with one patient in the self-expanding stent group (4%). During follow-up, percutaneous re-intervention related to the ductal stent was performed in five patients (17%) in the balloon-expandable stent group and seven patients (28%) in self-expanding stents group. Hybrid ductal stenting with self-expanding stents produced favourable results when compared with the results obtained with balloon-expandable stents. Immediate additional interventions and follow-up re-interventions were similar in both groups with complications more common in those with balloon-expandable stents.

  11. Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Baiwen Li

    Full Text Available Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.

  12. Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa-miR-29b-3p in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhao, Xiaohui; Liu, Yimin; Li, Zhihua; Zheng, Shangyou; Wang, Zairui; Li, Wenzhu; Bi, Zhuofei; Li, Liting; Jiang, Yanhui; Luo, Yuming; Lin, Qing; Fu, Zhiqiang; Rufu, Chen

    2018-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non-coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real-time PCR. Corresponding adjacent non-neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa-miR29b-3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up-regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up-regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa-miR-29b-3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by

  13. Heterogeneity index evaluated by slope of linear regression on 18F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Yong Joong; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June-Key; Kang, Keon Wook

    2017-01-01

    18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of 18 F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and 18 F-FDG PET/CT parameters. A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative 18 F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each 18 F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and 18 F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence. Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the 18 F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19-9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results

  14. Characterization of ductal carcinoma in situ on diffusion weighted breast MRI

    International Nuclear Information System (INIS)

    Rahbar, Habib; Partridge, Savannah C.; Eby, Peter R.; DeMartini, Wendy B.; Gutierrez, Robert L.; Peacock, Sue; Lehman, Constance D.

    2011-01-01

    To characterize ductal carcinoma in situ (DCIS) and its subtypes on diffusion-weighted imaging (DWI). We retrospectively reviewed 74 pure DCIS lesions in 69 women who underwent DWI at 1.5 T (b = 0 and 600 s/mm 2 ). Each lesion was characterized by qualitative DWI intensity, quantitative DWI lesion-to-normal contrast-to-noise ratio (CNR), and quantitative apparent diffusion coefficient (ADC). The detection rate was calculated with predetermined thresholds for each parameter. The effects of lesion size, grade, morphology, and necrosis were assessed. Ninety-six percent (71/74) of DCIS lesions demonstrated greater qualitative DWI intensity than normal breast tissue. Quantitatively, DCIS lesions demonstrated on average 56% greater signal than normal tissue (mean CNR = 1.83 ± 2.7) and lower ADC values (1.50 ± 0.28 x 10 -3 mm 2 /s) than normal tissue (2.01 ± 0.37 x 10 -3 mm 2 /s, p -3 mm 2 /s). Non-high-grade DCIS exhibited greater qualitative DWI intensity (p = 0.02) and quantitative CNR (p = 0.01) than high-grade DCIS but no difference in ADC (p = 0.40). Lesion size, morphology, and necrosis did not affect qualitative or quantitative DWI parameters of DCIS lesions (p > 0.05). DCIS lesions have higher DWI signal intensity and lower ADC values than normal breast tissue. DWI warrants further investigation as a potential non-contrast MRI tool for early breast cancer detection. (orig.)

  15. Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening.

    Science.gov (United States)

    Hur, Chin; Tramontano, Angela C; Dowling, Emily C; Brooks, Gabriel A; Jeon, Alvin; Brugge, William R; Gazelle, G Scott; Kong, Chung Yin; Pandharipande, Pari V

    2016-08-01

    Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

  16. Ductal Stent Implantation in Tetralogy of Fallot with Aortic Arch Abnormality

    Science.gov (United States)

    Ergul, Yakup; Saygi, Murat; Ozyilmaz, Isa; Guzeltas, Alper; Odemis, Ender

    2015-01-01

    Stenting of patent ductus arteriosus is an alternative to palliative cardiac surgery in newborns with duct-dependent or decreased pulmonary circulation; however, the use of this technique in patients with an aortic arch abnormality presents a challenge. Tetralogy of Fallot is a congenital heart defect that is frequently associated with anomalies of the aortic arch and its branches. The association is even more common in patients with chromosome 22q11 deletion. We present the case of an 18-day-old male infant who had cyanosis and a heart murmur. After an initial echocardiographic evaluation, the patient was diagnosed with tetralogy of Fallot and right-sided aortic arch. The pulmonary annulus and the main pulmonary artery and its branches were slightly hypoplastic; the ductus arteriosus was small. Conventional and computed tomographic angiograms revealed a double aortic arch and an aberrant left subclavian artery. The right aortic arch branched into the subclavian arteries and continued into the descending aorta, whereas the left aortic arch branched into the common carotid arteries and ended with the patent ductus arteriosus. After evaluation of the ductal anatomy, we implanted a 3.5 × 15-mm coronary stent in the duct. Follow-up injections showed augmented pulmonary flow and an increase in oxygen saturation from 65% to 94%. The patient was also found to have chromosome 22q11 deletion. PMID:26175649

  17. Glycogen synthase kinase-3β ablation limits pancreatitis-induced acinar-to-ductal metaplasia.

    Science.gov (United States)

    Ding, Li; Liou, Geou-Yarh; Schmitt, Daniel M; Storz, Peter; Zhang, Jin-San; Billadeau, Daniel D

    2017-09-01

    Acinar-to-ductal metaplasia (ADM) is a reversible epithelial transdifferentiation process that occurs in the pancreas in response to acute inflammation. ADM can rapidly progress towards pre-malignant pancreatic intraepithelial neoplasia (PanIN) lesions in the presence of mutant KRas and ultimately pancreatic adenocarcinoma (PDAC). In the present work, we elucidate the role and related mechanism of glycogen synthase kinase-3beta (GSK-3β) in ADM development using in vitro 3D cultures and genetically engineered mouse models. We show that GSK-3β promotes TGF-α-induced ADM in 3D cultured primary acinar cells, whereas deletion of GSK-3β attenuates caerulein-induced ADM formation and PanIN progression in Kras G12D transgenic mice. Furthermore, we demonstrate that GSK-3β ablation influences ADM formation and PanIN progression by suppressing oncogenic KRas-driven cell proliferation. Mechanistically, we show that GSK-3β regulates proliferation by increasing the activation of S6 kinase. Taken together, these results indicate that GSK-3β participates in early pancreatitis-induced ADM and thus could be a target for the treatment of chronic pancreatitis and the prevention of PDAC progression. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Hepatocyte growth factor signaling in intrapancreatic ductal cells drives pancreatic morphogenesis.

    Directory of Open Access Journals (Sweden)

    Ryan M Anderson

    Full Text Available In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908 , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.

  19. ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.

    Science.gov (United States)

    Perkhofer, Lukas; Schmitt, Anna; Romero Carrasco, Maria Carolina; Ihle, Michaela; Hampp, Stephanie; Ruess, Dietrich Alexander; Hessmann, Elisabeth; Russell, Ronan; Lechel, André; Azoitei, Ninel; Lin, Qiong; Liebau, Stefan; Hohwieler, Meike; Bohnenberger, Hanibal; Lesina, Marina; Algül, Hana; Gieldon, Laura; Schröck, Evelin; Gaedcke, Jochen; Wagner, Martin; Wiesmüller, Lisa; Sipos, Bence; Seufferlein, Thomas; Reinhardt, Hans Christian; Frappart, Pierre-Olivier; Kleger, Alexander

    2017-10-15

    Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576-90. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Second pancreatectomy for recurrent pancreatic ductal adenocarcinoma in the remnant pancreas: A pooled analysis.

    Science.gov (United States)

    Zhou, Yanming; Song, Ailing; Wu, Lupeng; Si, Xiaoying; Li, Yumin

    The aim of this study was to examine the outcomes of second pancreatectomy for the treatment of recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. Search of the PubMed database was undertaken to identify relevant English language studies. Pooled individually data were examined for clinical outcomes after second pancreatectomy for recurrent PDAC. A total of 19 articles involving 55 patients were eligible for inclusion. The median disease-free interval after initial resection was 33 (range 7-143) months. Of the 55 patients reported, 52 (94.5%) patients underwent completion total pancreatectomy in the second operation for recurrences, including 15 patients who developed recurrences more than 5 years after the initial operation. There was no perioperative death. The 1-, 3- and 5-year overall survival rate after the second pancreatectomy was 82.2%, 49.2% and 40.6% respectively. Second pancreatectomy for recurrent PDAC can be performed safely with long-term survival in selected patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  1. An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

    Science.gov (United States)

    Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

    2012-10-01

    We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

  2. No miR quirk: dysregulation of microRNAs in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Cheung, Philip Y; Szafranska-Schwarzbach, Anna E; Schlageter, Annette M; Andruss, Bernard F; Weiss, Glen J

    2012-01-01

    MicroRNAs are post-transcriptional regulators of gene expression with tissue-specific expression profiles. Dysregulation of microRNAs has been shown to play a role in carcinogenesis. Although progress has been made in the diagnosis and treatment of many cancers, pancreatic cancer remains an intractable public health problem, causing 6.58% of cancer deaths despite making up less than 3% of cancer diagnoses in the United States. No screening, diagnostic or imaging techniques exist with the sensitivity to detect pancreatic cancer in its early, operable stages. Risk factors include numerous inherited syndromes, diabetes mellitus, and hepatitis C virus infection. Here we review the literature regarding dysregulation of microRNA expression in native pancreas, pancreatic ductal adenocarcinoma (the dominant form of pancreatic cancer), and its risk factors to illuminate the biology and progression of this disease. We explore promising evidence for the use of microRNAs as prognostic and diagnostic tools, and discuss emerging reports on microRNA therapeutics.

  3. Ductal carcinoma in situ (DCIS) of the breast: the need for psychosocial research.

    Science.gov (United States)

    Carrera, C; Payne, S

    1999-01-01

    Since the introduction of the National Health Service Breast Screening Programme (NHSBSP), the number of ductal carcinoma in situ (DCIS) cases has increased considerably. Despite its increased incidence, some NHS leaflets and reports do not mention it, and the general public seems largely unaware of its existence. There are numerous biological studies dealing with this condition, but its psychosocial aspects seem to have been neglected. We have only been able to locate two British studies (Farmer, A. 1996. Unpublished PhD thesis, University of Southampton; Webb, C. and Koch, T. 1997. J. Adv. Nurs., 25, 154-525) that address some of the psychosocial issues associated with DCIS. This paper starts by defining DCIS and explaining its usual presentation, natural history and epidemiology. The treatment options for DCIS are described, together with the great deal of confusion and lack of agreement that accompanies them. The psychological issues that women with screen-detected DCIS have to deal with are different from those affecting women diagnosed with symptomatic breast cancer, and a summary of these issues is given. Finally, some suggestions for future psychosocial research are provided. Because the UK as a whole was not covered by the NHSBSP until 1990 (Baum, M. 1995. Lancet, 346, 436; Gage and Fouquet, 1997), the main focus will be on papers published from that year onwards, although some key papers published before then will also be included. The papers reviewed here were found in MEDLINE, EMBASE and BIDS (ISI). Copyright 1999 John Wiley & Sons, Ltd.

  4. Paradigm Shift toward Reducing Overtreatment of Ductal Carcinoma In Situ of Breast

    Directory of Open Access Journals (Sweden)

    Yasuaki Sagara

    2017-08-01

    Full Text Available The prevalence of ductal carcinoma in situ (DCIS of the breast has increased substantially after the introduction of breast cancer screening programs, although the clinical effects of early DCIS detection and treatment remain unclear. The standard treatment for DCIS has involved local breast-conserving surgery (BCS followed by radiotherapy (RT or total mastectomy with/without endocrine therapy, and the choice of local treatment is not usually based on clinicopathologic or biological factors. However, we have investigated the effectiveness of local treatment using breast surgery and RT using Surveillance, Epidemiology, and End Results data, and found that the effectiveness of breast surgery was modified by the nuclear grade. Furthermore, breast cancer-specific survival was identical between patients with low-grade DCIS who did and did not undergo surgery. Moreover, we found that RT after BCS for DCIS was only associated with a survival benefit among patients with risk factors for local recurrence, such as nuclear grade, age, and tumor size. Ongoing clinical trials and translational research have attempted to develop a treatment strategy that prevents the overdiagnosis and overtreatment of low-risk DCIS, as well as a biology-based treatment strategy for using targeted therapy. Therefore, to develop a tailored treatment strategy for DCIS, we need to identify molecular and biological classifications based on the results from translational research, national databases, and clinical trials.

  5. Gastro-pancreaticojejunostomy for treatment of pancreatic ductal obstruction in a post-Whipple procedure patient.

    Science.gov (United States)

    Rodrigues-Pinto, Eduardo; Grimm, Ian S; Baron, Todd H

    2015-01-01

    We report a case of a woman with a medical history of classic Whipple surgery who underwent endoscopic ultrasound (EUS)-guided pancreatic drainage due to smouldering acute pancreatitis secondary to an obstructing pancreatic ductal stone. A gastro-pancreaticojejunostomy anastomosis was created anterogradely, with dilation of both the anastomoses in the same procedure, with subsequent decompression of the pancreatic duct. Endoscopic retrograde pancreatography (ERP) is often impossible to perform in patients with post-Whipple procedure anatomy due to inaccessibility to the pancreaticojejunostomy anastomosis. EUS-guided pancreatic drainage may be offered in these patients in whom the pancreatic duct cannot be accessed at ERP. It has been used as a platform for access to and drainage of the pancreatic duct either by rendezvous or transmural drainage. However, only one of four patients achieve successful completion of the rendezvous procedure. There are limited data regarding safety and long-term outcome of this procedure, as well as scant guidelines on the optimal time for leaving stents in place. We believe definitive endoscopic therapy should be attempted, whenever possible, after relief of obstruction. In our case, we expect that stent occlusion is inevitable and that long-term drainage is possible due to drainage occurring between the stent and the stone.

  6. The management of ductal carcinoma in situ in North America and Europe. Results of a survey.

    Science.gov (United States)

    Ceilley, Elizabeth; Jagsi, Reshma; Goldberg, Saveli; Kachnic, Lisa; Powell, Simon; Taghian, Alphonse

    2004-11-01

    The goal of the current study was to understand and document contemporary treatment approaches in the management of ductal carcinoma in situ (DCIS). An original questionnaire was designed to assess radiation oncologists' management of breast carcinoma, including 26 questions specifically addressing DCIS. A postal survey was conducted of members of the American and European Societies of Therapeutic Radiology and Oncology. The results of 702 responses from North America were compared with 435 responses from Europe, to determine treatment recommendations and variability by type of institution and geographic region. There were strong correlations between the grade of DCIS and/or the margin status and the use of radiotherapy (RT; P variations in physician recommendations for tamoxifen (P < 0.001), but not in the tendency to recommend RT. North American academic physicians were less likely to recommend RT for favorable DCIS than nonacademic physicians (P < 0.01). There were marked differences in physician opinions regarding the management of DCIS, with significant international differences in patterns of care. The survey quantified and highlighted areas of agreement and controversy regarding the use of RT and tamoxifen in the management of DCIS. It provided support for large international trials to evaluate the optimal management of DCIS in the areas identified as most controversial.

  7. Low Expression of TBX4 Predicts Poor Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Meijuan Zong

    2011-08-01

    Full Text Available This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4, a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3% expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010. In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

  8. Gamma Imaging-Guided Minimally Invasive Breast Biopsy: Initial Clinical Experience.

    Science.gov (United States)

    Brem, Rachel F; Mehta, Anita K; Rapelyea, Jocelyn A; Akin, Esma A; Bazoberry, Adriana M; Velasco, Christel D

    2018-03-01

    The purpose of this study was to evaluate our initial experience with gamma imaging-guided vacuum-assisted breast biopsy in women with abnormal findings. A retrospective review of patients undergoing breast-specific gamma imaging (BSGI), also known as molecular breast imaging (MBI), between April 2011 and October 2015 found 117 nonpalpable mammographically and sonographically occult lesions for which gamma imaging-guided biopsies were recommended. Biopsy was performed with a 9-gauge vacuum-assisted device with subsequent placement of a titanium biopsy site marker. Medical records and pathologic findings were evaluated. Of the 117 biopsies recommended, 104 were successful and 13 were canceled. Of the 104 performed biopsies, 32 (30.8%) had abnormal pathologic findings. Of those 32 biopsies, nine (28.1%) found invasive cancers, six (18.8%) found ductal carcinoma in situ (DCIS), and 17 (53.1%) found high-risk lesions. Of the 17 high-risk lesions, there were three (17.6%) lobular carcinomas in situ, five (29.4%) atypical ductal hyperplasias, two (11.8%) atypical lobular hyperplasias, one (5.9%) flat epithelial atypia, and six (35.3%) papillomas. Two cases of atypical ductal hyperplasia were upgraded to DCIS at surgery. The overall cancer detection rate for gamma imaging-guided biopsy was 16.3%. In this study, gamma imaging-guided biopsy had a positive predictive value of total successful biopsies of 16.3% for cancer and 30.8% for cancer and high-risk lesions. Gamma imaging-guided biopsy is a viable approach to sampling BSGI-MBI-detected lesions without sonographic or mammographic correlate. Our results compare favorably to those reported for MRI-guided biopsy.

  9. RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2011-07-28

    We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70\\/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.

  10. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

    Science.gov (United States)

    Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

    2018-04-26

    Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

  11. Conservative treatment for invasive lobular carcinoma of the breast

    International Nuclear Information System (INIS)

    Dilhuydy, Jean-Marie; Salem, Naji; Durand, Michel; Prie, Loiec; Stoeckle, Eberhard; Benyoucef, Ahmed; Dilhuydy, Marie-Helene

    1997-01-01

    Purpose/Objective: To evaluate the place of conservative treatment in invasive lobular carcinoma. Materials and Methods: From 01/01/85 to 31/12/92, 109 patients with clinically and mammographically unifocal invasive lobular carcinoma of the breast (T<35 mm) underwent tumorectomy, axillary dissection and radiation therapy; they received an adjuvant treatment in case of nodal involvement (n = 31) or lack of estrogen and progesterone receptors (n = 16). The entire breast received 50 Gy with a systematic boost of 10 Gy. Results: With a median follow-up of 86 months, we observed 11 isolated local recurrences (T0 = (3(19)), T1 = (6(41)), T2 = (2(49))), 7 local recurrences associated with metastases (T1 = (3(41)), T2 = (4(49))) and 7 cases of metastatic diseases (T1 = (4(41)), T2 = (3(49))). Among the 11 patients with isolated local recurrence, 7 are alive with no evidence of disease after salvage mastectomy. Nine contro-lateral breast cancers occurred, 2 synchronous and 7 metachronous. The 5-year actuarial local relapse free survival, metastase free survival and overall survival are respectively 87.3%, 89.5% and 92.5%, whatever histological subtypes. These results are comparable to those obtained in 1393 cases of infiltrating ductal carcinoma similarly treated during the same period in our institute, except for local relapse (87.3% vs 91%, p = 0.008). Conclusion: Conservative treatment for invasive lobular carcinoma of the breast (T<35 mm) is appropriate in the absence of clinical or mammographic multifocality

  12. Clinicopathological study of rare invasive epithelial tumors of breast: An institutional study

    Directory of Open Access Journals (Sweden)

    Karthik Kasireddy

    2016-01-01

    Full Text Available Introduction: Invasive breast cancer (BC is the most common carcinoma in women. It accounts for 22% of all female cancers. Most tumors are derived from mammary duct epithelium, and up to 75% of BCs are ductal carcinomas. The second most common tumor is invasive lobular carcinoma. However, there are many variants which are less common but well defined by the World Health Organization classification. They comprise <10% of breast tumors. Their clinical behavior differs greatly. Hence, it is important to know their main histomorphological features to make the best treatment of choice and to foresee prognosis. Aims and Objectives: To study the histomorphological features, incidence, and clinical features of rare invasive epithelial tumors of the breast. Materials and Methods: This study was done in the department of pathology, Sri Devaraj Urs Medical College, Kolar. All the neoplastic breast lesions over a period of 5 years (July 2010-September 2015 are included in the study. Clinical features and other details (estrogen receptor/progesterone receptor, human epidermal receptor-2, lymph nodes are obtained from the department (surgery records. Specimens are received and preserved in 10% formalin and are subjected to routine histopathological processing. Hematoxylin and eosin sections are studied, and a morphological diagnosis is given. All rare invasive epithelial breast tumors will be reviewed meticulously. Results and Conclusion: A total number of invasive epithelial tumors of breast were 105. The most common presenting symptom was breast lump. Rare invasive epithelial breast tumors account to 28.5%. The age range from 15 to 70 years. Most common, rare invasive epithelial tumor in our study is medullary carcinoma. Hence, it is imperative to always maintain a Hawks vigil during microscopic diagnosis to know prognosis of the condition and to facilitate early and prompt treatment to the patient.

  13. Long-term outcomes of ductal carcinoma in situ of the breast: a systematic review, meta-analysis and meta-regression analysis

    International Nuclear Information System (INIS)

    Stuart, Kirsty E.; Houssami, Nehmat; Taylor, Richard; Hayen, Andrew; Boyages, John

    2015-01-01

    To summarize data on long-term ipsilateral local recurrence (LR) and breast cancer death rate (BCDR) for patients with ductal carcinoma in situ (DCIS) who received different treatments. Systematic review and study-level meta-analysis of prospective (n = 5) and retrospective (n = 21) studies of patients with pure DCIS and with median or mean follow-up time of ≥10 years. Meta-regression was performed to assess and adjust for effects of potential confounders – the average age of women, period of initial treatment, and of bias – follow-up duration on recurrence- and death-rates in each treatment group. LR and BCDR rates by local treatment used were reported. Outside of randomized trials, remaining studies were likely to have tailored patient treatment according to the clinical situation. Nine thousand four hundred and four DCIS cases in 9391 patients with 10-year follow-up were included. The adjusted meta-regression LR rate for mastectomy was 2.6 % (95 % CI, 0.8–4.5); breast-conserving surgery with radiotherapy (RT), 13.6 % (95 % CI, 9.8–17.4); breast-conserving surgery without RT, 25.5 % (95 % CI, 18.1–32.9); and biopsy-only (residual predominately low-grade DCIS following inadequate excision), 27.8 % (95 % CI, 8.4–47.1). RT + tamoxifen (TAM) in conservation surgery (CS) patients resulted in lower LR compared to one or no adjuvant treatments: LR rate for CS + RT + TAM, 9.7 %; CS + RT(no TAM), 14.1 %; CS + TAM(no RT), 24.7 %; CS(alone), 25.1 % (linear trend for treatment P < 0.0001). Compared to CS + RT + TAM, a significantly higher invasive LR was observed for CS(alone), odds ratio (OR) 2.61 (P < 0.0001); CS + TAM(no RT), OR 2.52 (P = 0.001); CS + RT(no TAM), OR 1.59 (P = 0.022). BCDR was similar for mastectomy, breast-conserving surgery with or without RT (1.3–2.0 %) and non-significantly higher for biopsy-only (2.7 %). Additionally, the 15-year follow-up was reported where all like-studies had ≥ 15-year data sets; the biopsy-only patients had a

  14. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    Science.gov (United States)

    2017-11-15

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  15. Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.

    Science.gov (United States)

    Sun, Xiangjie; Zuo, Ke; Huang, Dan; Yu, Baohua; Cheng, Yufan; Yang, Wentao

    2017-07-11

    Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare. We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast. To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

  16. Non-invasively predicting differentiation of pancreatic cancer through comparative serum metabonomic profiling.

    Science.gov (United States)

    Wen, Shi; Zhan, Bohan; Feng, Jianghua; Hu, Weize; Lin, Xianchao; Bai, Jianxi; Huang, Heguang

    2017-11-02

    The differentiation of pancreatic ductal adenocarcinoma (PDAC) could be associated with prognosis and may influence the choices of clinical management. No applicable methods could reliably predict the tumor differentiation preoperatively. Thus, the aim of this study was to compare the metabonomic profiling of pancreatic ductal adenocarcinoma with different differentiations and assess the feasibility of predicting tumor differentiations through metabonomic strategy based on nuclear magnetic resonance spectroscopy. By implanting pancreatic cancer cell strains Panc-1, Bxpc-3 and SW1990 in nude mice in situ, we successfully established the orthotopic xenograft models of PDAC with different differentiations. The metabonomic profiling of serum from different PDAC was achieved and analyzed by using 1 H nuclear magnetic resonance (NMR) spectroscopy combined with the multivariate statistical analysis. Then, the differential metabolites acquired were used for enrichment analysis of metabolic pathways to get a deep insight. An obvious metabonomic difference was demonstrated between all groups and the pattern recognition models were established successfully. The higher concentrations of amino acids, glycolytic and glutaminolytic participators in SW1990 and choline-contain metabolites in Panc-1 relative to other PDAC cells were demonstrated, which may be served as potential indicators for tumor differentiation. The metabolic pathways and differential metabolites identified in current study may be associated with specific pathways such as serine-glycine-one-carbon and glutaminolytic pathways, which can regulate tumorous proliferation and epigenetic regulation. The NMR-based metabonomic strategy may be served as a non-invasive detection method for predicting tumor differentiation preoperatively.

  17. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  18. 53. Bilateral ductal stenting for nonconfluent pulmonary arteries in a newborn

    Directory of Open Access Journals (Sweden)

    K. Al Dhahri

    2016-07-01

    Full Text Available Bilateral PDA dependent pulmonary circulation with right and left pulmonary artery discontinuity is very rare. Limited data available for bilateral PDA stenting. Bilateral PDA stenting in nonconfluent pulmonary arteries is challenging procedure but can be considered as an option in the management of complex conditions like this. 12 days old Preterm (36 weeks gestation male baby with birth weight of 2.6 kg developed respiratory distress with severe cyanosis and desaturation upto 50%. Baby was intubated and started on Prostaglandin 0.05 mic/kg/mt. His saturation improved to 80%. Echocardiogram showed complex cyanotic heart disease, Situs ambiguous, dextrocardia, complete unbalanced AV septal defect, pulmonary atresia , nonconfluent small branch pulmonary arteries supplied by the bilateral patent ductus arteriosus (PDA from right aortic arch and all four pulmonary veins form a confluence and drain into superior vena cava(SVC through vertical vein with no obstruction. Baby was taken up for PDA stenting. descending aortogram showed right aortic arch with vertical tortuous duct to right pulmonary artery (RPA and another short duct with acute angle from left subclavian artery to left pulmonary artery (LPA . Both ducti stented with coronary stents. Vertical vein angiogram showed both lungs drain to a confluence and then to SVC via ascending vertical vein with no obstruction. After stenting lung perfusion improved and the baby was stable and maintained 80% saturation on room air. Bilateral PDA dependent pulmonary circulation with right and left pulmonary artery discontinuity is very rare. Our case is unique with Heterotaxy, TAPVC, Dextrocardia and double ducti. Eventhough bilateral ductal stenting is technically challenging it is successful through femoral artery approach.

  19. Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

    International Nuclear Information System (INIS)

    Shaitelman, Simona F.; Grills, Inga S.; Kestin, Larry L.; Ye Hong; Nandalur, Sirisha; Huang Jiayi; Vicini, Frank A.

    2011-01-01

    Purpose: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. Methods and Materials: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age ± 2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p = 0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p = 0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p = 0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Conclusions: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

  20. Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma.

    Science.gov (United States)

    DuFort, Christopher C; DelGiorno, Kathleen E; Hingorani, Sunil R

    2016-06-01

    The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit. The high concentration in the stroma of the glycosaminoglycan hyaluronan, together with the large gel-fluid phase and pressures it generates, were recently identified as primary sources of treatment resistance in pancreas cancer. Whereas the relatively minor role of free interstitial fluid in the fluid mechanics and perfusion of tumors has been long appreciated, the less mobile, gel-fluid phase has been largely ignored for historical and technical reasons. The inability of classic methods of fluid pressure measurement to capture the gel-fluid phase, together with a dependence on xenograft and allograft systems that inaccurately model tumor vascular biology, has led to an undue emphasis on the role of free fluid in impeding perfusion and drug delivery and an almost complete oversight of the predominant role of the gel-fluid phase. We propose that a hyaluronan-rich, relatively immobile gel-fluid phase induces vascular collapse and hypoperfusion as a primary mechanism of treatment resistance in pancreas cancers. Similar properties may be operant in other solid tumors as well, so revisiting and characterizing fluid mechanics with modern techniques in other autochthonous cancers may be warranted. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

    Science.gov (United States)

    Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

    2018-03-16

    Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  2. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice

    Directory of Open Access Journals (Sweden)

    Kayla A. Quirin

    2018-03-01

    Full Text Available Recombinant adeno-associated virus (rAAV-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9 expressing GFP in a self-complementary (sc AAV vector under an EF1α promoter (scAAV.GFP following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg. Intraductal delivery of 1 × 1011 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 1011 vg. In a KrasG12D-driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  3. Use of imaging during symptomatic follow-up after resection of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Groot, Vincent P; Daamen, Lois A; Hagendoorn, Jeroen; Borel Rinkes, Inne H M; van Santvoort, Hjalmar C; Molenaar, I Quintus

    2018-01-01

    Controversy exists whether follow-up after resection of pancreatic ductal adenocarcinoma (PDAC) should include standardized imaging for the detection of disease recurrence. The purpose of this study was to evaluate how often patients undergo imaging in a setting where routine imaging is not performed. Secondly, the pattern, timing, and treatment of recurrent PDAC were assessed. This was a post hoc analysis of a prospective database of all consecutive patients undergoing pancreatic resection of PDAC between January 2011 and January 2015. Data on imaging procedures during follow-up, recurrence location, and treatment for recurrence were extracted and analyzed. Associations between clinical characteristics and post-recurrence survival were assessed with the log-rank test and Cox univariable and multivariable proportional hazards models. A total of 85 patients were included. Seventy-four patients (87%) underwent imaging procedures during follow-up at least once, with a mean amount of 3.1 ± 1.9 imaging procedures during the entire follow-up period. Sixty-eight patients (80%) were diagnosed with recurrence, 58 (85%) of whom after the manifestation of clinical symptoms. Additional tumor-specific treatment was administered in 17 of 68 patients (25%) with recurrence. Patients with isolated local recurrence, treatment after recurrence, and a recurrence-free survival >10 mo had longer post-recurrence survival. Even though a symptomatic follow-up strategy does not include routine imaging, the majority of patients with resected PDAC underwent additional imaging procedures during their follow-up period. Further prospective studies are needed to determine the actual clinical value, psychosocial implications, and cost-effectiveness of different forms of follow-up after resection of PDAC. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges.

    Science.gov (United States)

    Root, Alex; Allen, Peter; Tempst, Paul; Yu, Kenneth

    2018-03-07

    Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but interdisciplinary

  5. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Alex Root

    2018-03-01

    Full Text Available Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but

  6. Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis.

    Science.gov (United States)

    Attiyeh, Marc A; Chakraborty, Jayasree; Doussot, Alexandre; Langdon-Embry, Liana; Mainarich, Shiana; Gönen, Mithat; Balachandran, Vinod P; D'Angelica, Michael I; DeMatteo, Ronald P; Jarnagin, William R; Kingham, T Peter; Allen, Peter J; Simpson, Amber L; Do, Richard K

    2018-04-01

    Pancreatic cancer is a highly lethal cancer with no established a priori markers of survival. Existing nomograms rely mainly on post-resection data and are of limited utility in directing surgical management. This study investigated the use of quantitative computed tomography (CT) features to preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC) patients. A prospectively maintained database identified consecutive chemotherapy-naive patients with CT angiography and resected PDAC between 2009 and 2012. Variation in CT enhancement patterns was extracted from the tumor region using texture analysis, a quantitative image analysis tool previously described in the literature. Two continuous survival models were constructed, with 70% of the data (training set) using Cox regression, first based only on preoperative serum cancer antigen (CA) 19-9 levels and image features (model A), and then on CA19-9, image features, and the Brennan score (composite pathology score; model B). The remaining 30% of the data (test set) were reserved for independent validation. A total of 161 patients were included in the analysis. Training and test sets contained 113 and 48 patients, respectively. Quantitative image features combined with CA19-9 achieved a c-index of 0.69 [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9, imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test data. We present two continuous survival prediction models for resected PDAC patients. Quantitative analysis of CT texture features is associated with overall survival. Further work includes applying the model to an external dataset to increase the sample size for training and to determine its applicability.

  7. Clinical impact of sarcopenia on prognosis in pancreatic ductal adenocarcinoma: A retrospective cohort study.

    Science.gov (United States)

    Ninomiya, Go; Fujii, Tsutomu; Yamada, Suguru; Yabusaki, Norimitsu; Suzuki, Kojiro; Iwata, Naoki; Kanda, Mitsuro; Hayashi, Masamichi; Tanaka, Chie; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2017-03-01

    To investigate the impact of the body composition such as skeletal muscle, visceral fat and body mass index (BMI) on patients with resected pancreatic ductal adenocarcinoma (PDAC). A total of 265 patients who underwent curative surgery for PDAC were examined in this study. The total skeletal muscle and fat tissue areas were evaluated in a single image obtained at the third lumber vertebra during a preoperative computed tomography (CT) scan. The patients were assigned to either the sarcopenia or non-sarcopenia group based on their skeletal muscle index (SMI) and classified into high visceral fat area (H-VFA) or low VFA (L-VFA) groups. The association of clinicopathological features and prognosis with the body composition were statistically analyzed. There were 170 patients (64.2%) with sarcopenia. The median survival time (MST) was 23.7 months for sarcopenia patients and 25.8 months for patients without sarcopenia. The MST was 24.4 months for H-VFA patients and 25.8 months for L-VFA patients. However, sarcopenia patients with BMI ≥22 exhibited significantly poorer survival than patients without sarcopenia (MST: 19.2 vs. 35.4 months, P = 0.025). There was a significant difference between patients with and without sarcopenia who did not receive chemotherapy (5-year survival rate: 0% vs. 68.3%, P = 0.003). The multivariate analysis revealed that tumor size, positive dissected peripancreatic tissue margin, and sarcopenia were independent prognostic factors. Sarcopenia is an independent prognostic factor in PDAC patients with a BMI ≥22. Therefore, evaluating skeletal muscle mass may be a simple and useful approach for predicting patient prognosis. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  8. Intratumoral heterogeneity of 18F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Hyun, Seung Hyup; Kim, Ho Seong; Lee, Kyung-Han; Kim, Byung-Tae; Choi, Joon Young; Choi, Seong Ho; Choi, Dong Wook; Lee, Jong Kyun; Lee, Kwang Hyuck; Park, Joon Oh

    2016-01-01

    To assess whether intratumoral heterogeneity measured by 18 F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment 18 F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. Intratumoral heterogeneity of 18 F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters. (orig.)

  9. Missed pancreatic ductal adenocarcinoma: Assessment of early imaging findings on prediagnostic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Kyung Mi; Kim, Seong Hyun, E-mail: sh6453.kim@samsung.com; Kim, Young Kon; Song, Kyoung Doo; Lee, Soon Jin; Choi, Dongil

    2015-08-15

    Highlights: • MR imaging was superior to CT for the detection of early PDAC. • A focal lesion with no MPD interruption is common MR finding of early PDAC. • A mean volume doubling time of early PDAC was about five months. - Abstract: Objective: To investigate the early imaging findings and growth rate of pancreatic ductal adenocarcinoma (PDAC), and to assess whether MR imaging detects early PDAC better than CT. Materials and methods: The institutional review board approved this retrospective study and waived the requirement for informed consent. Twenty-two patients were included, and two radiologists, by consensus, assessed the presence of focal lesions, interruption of the main pancreatic duct (MPD), MPD dilatation, and pancreatitis, volume doubling time (VDT) of PDAC on prediagnostic MR imaging. Two other observers independently reviewed three image sets (CT images, unenhanced MR images, and unenhanced and contrast-enhanced MR images) for the detection of early PDAC. Paired Wilcoxon signed rank test and receiver operating characteristic (ROC) curve analysis were used for statistical analyses. Results: In 20 (90.9%) patients, prediagnostic MR exams showed abnormality, and all of them showed focal lesions on the first abnormal prediagnostic MR exams. Thirteen lesions (65%) showed no MPD interruption and one lesion (5%) was accompanied by pancreatitis. The mean VDT of PDAC was 151.7 days (range, 18.3–417.8 days). Diagnostic performance of unenhanced MR images (Az, 0.971–0.989) and combined unenhanced and contrast-enhanced MR images (Az, 0.956–0.963) was significantly better than that of CT images (Az, 0.565–0.583; p < 0.01) for both observers, Conclusion: The most common early imaging finding of PDAC on prediagnostic MR exams was a focal lesion with no MPD interruption with a mean volume doubling time of five months. MR imaging was superior to CT for the detection of early PDAC.

  10. Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, Andrea M.; Portschy, Pamela R. [Division of Surgical Oncology, University of Minnesota, Minneapolis, Minnesota (United States); Lee, Chung [Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota (United States); Le, Chap T. [Division of Biostatistics, University of Minnesota, Minneapolis, Minnesota (United States); Han, Linda K. [Department of Surgery, Indiana University, Indianapolis, Indiana (United States); Washington, Tara [Vantage Oncology, Redhawk and Wildomar Centers California, Wildomar, California (United States); Kinney, Michael [Center for Advanced Breast Care, Arlington Heights, Illinois (United States); Bretzke, Margit [Surgical Specialists of Minnesota, Minneapolis, Minnesota (United States); Tuttle, Todd M., E-mail: tuttl006@umn.edu [Division of Surgical Oncology, University of Minnesota, Minneapolis, Minnesota (United States)

    2013-11-01

    Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.

  11. Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

    International Nuclear Information System (INIS)

    Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung; Le, Chap T.; Han, Linda K.; Washington, Tara; Kinney, Michael; Bretzke, Margit; Tuttle, Todd M.

    2013-01-01

    Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatment in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended

  12. A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Jeran K Stratford

    2010-07-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC remains a lethal disease. For patients with localized PDAC, surgery is the best option, but with a median survival of less than 2 years and a difficult and prolonged postoperative course for most, there is an urgent need to better identify patients who have the most aggressive disease.We analyzed the gene expression profiles of primary tumors from patients with localized compared to metastatic disease and identified a six-gene signature associated with metastatic disease. We evaluated the prognostic potential of this signature in a training set of 34 patients with localized and resected PDAC and selected a cut-point associated with outcome using X-tile. We then applied this cut-point to an independent test set of 67 patients with localized and resected PDAC and found that our signature was independently predictive of survival and superior to established clinical prognostic factors such as grade, tumor size, and nodal status, with a hazard ratio of 4.1 (95% confidence interval [CI] 1.7-10.0. Patients defined to be high-risk patients by the six-gene signature had a 1-year survival rate of 55% compared to 91% in the low-risk group.Our six-gene signature may be used to better stage PDAC patients and assist in the difficult treatment decisions of surgery and to select patients whose tumor biology may benefit most from neoadjuvant therapy. The use of this six-gene signature should be investigated in prospective patient cohorts, and if confirmed, in future PDAC clinical trials, its potential as a biomarker should be investigated. Genes in this signature, or the pathways that they fall into, may represent new therapeutic targets. Please see later in the article for the Editors' Summary.

  13. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Luigi Laghi

    Full Text Available Pancreatic cancer risk is increased in Lynch syndrome (LS patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI. However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27 in 338 consecutive pancreatic ductal adenocarcinoma (PDAC, resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.Only one PDAC (0.3% showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5% LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.

  14. Bile ductal injury and ductular reaction are frequent phenomena with different significance in autoimmune hepatitis.

    Science.gov (United States)

    Verdonk, Robert C; Lozano, Mallaki F; van den Berg, Aad P; Gouw, Annette S H

    2016-09-01

    The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis. Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction. Thirty-five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post-treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases. Bile duct injury and ductular reaction are very common in newly diagnosed autoimmune hepatitis and cannot be predicted biochemically. Bile duct injury may subside in the majority of treated AIH cases while DR tends to persist during follow up. These findings show that the two phenomena are part of the spectrum of AIH with dissimilar responses to treatment and do not necessarily point towards an overlap syndrome. Persistence of ductular reaction after treatment supports the notion that it represents a regenerative response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017.

    Science.gov (United States)

    Isaji, Shuji; Mizuno, Shugo; Windsor, John A; Bassi, Claudio; Fernández-Del Castillo, Carlos; Hackert, Thilo; Hayasaki, Aoi; Katz, Matthew H G; Kim, Sun-Whe; Kishiwada, Masashi; Kitagawa, Hirohisa; Michalski, Christoph W; Wolfgang, Christopher L

    2018-01-01

    This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19-9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight

  16. X-ray phase-contrast CT of a pancreatic ductal adenocarcinoma mouse model.

    Directory of Open Access Journals (Sweden)

    Arne Tapfer

    Full Text Available To explore the potential of grating-based x-ray phase-contrast computed tomography (CT for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i high-resolution synchrotron radiation (SR imaging and ii dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i high-performance imaging for virtual microscopy applications and ii biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR of selected regions of interest (ROI in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications.

  17. Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne Vibeke

    2015-01-01

    Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessita......Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer...... progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each...

  18. Exotic invasive plants

    Science.gov (United States)

    Carolyn Hull Sieg; Barbara G. Phillips; Laura P. Moser

    2003-01-01

    Ecosystems worldwide are threatened by nonnative plant invasions that can cause undesirable, irreversible changes. They can displace native plants and animals, out-cross with native flora, alter nutrient cycling and other ecosystem functions, and even change an ecosystem's flammability (Walker and Smith 1997). After habitat loss, the spread of exotic species is...

  19. Minimally invasive distal pancreatectomy

    NARCIS (Netherlands)

    Røsok, Bård I.; de Rooij, Thijs; van Hilst, Jony; Diener, Markus K.; Allen, Peter J.; Vollmer, Charles M.; Kooby, David A.; Shrikhande, Shailesh V.; Asbun, Horacio J.; Barkun, Jeffrey; Besselink, Marc G.; Boggi, Ugo; Conlon, Kevin; Han, Ho Seong; Hansen, Paul; Kendrick, Michael L.; Kooby, David; Montagnini, Andre L.; Palanivelu, Chinnasamy; Wakabayashi, Go; Zeh, Herbert J.

    2017-01-01

    The first International conference on Minimally Invasive Pancreas Resection was arranged in conjunction with the annual meeting of the International Hepato-Pancreato-Biliary Association (IHPBA), in Sao Paulo, Brazil on April 19th 2016. The presented evidence and outcomes resulting from the session

  20. Pathogenesis of invasive candidiasis.

    NARCIS (Netherlands)

    Veerdonk, F.L. van de; Kullberg, B.J.; Netea, M.G.

    2010-01-01

    PURPOSE OF REVIEW: Disseminated candidiasis remains a life-threatening disease in the ICU. The development of invasive disease with Candida albicans is dependent on multiple factors, such as colonization and efficient host defense at the mucosa. In the present review, we describe the host defense

  1. A High Ductal Flow Velocity Is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22–27 Weeks Gestational Age

    Science.gov (United States)

    Olsson, Karl Wilhelm; Jonzon, Anders; Sindelar, Richard

    2012-01-01

    Objective. To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22–27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors. Method. Infants born at 22–27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory, and outcome parameters. Echocardiographic examinations during treatment were reviewed. Results. Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25 + 4 weeks versus 24 + 3 weeks; P = 0.047), and a higher pretreatment left to right maximal ductal flow velocity (1.6 m/s versus 1.1 m/s; P = 0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at start of treatment, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04; P = 0.049). Conclusion. Maximal ductal flow velocity was independently associated with success of PDA treatment. PMID:23316351

  2. A High Ductal Flow Velocity Is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22–27 Weeks Gestational Age

    Directory of Open Access Journals (Sweden)

    Karl Wilhelm Olsson

    2012-01-01

    Full Text Available Objective. To identify factors affecting closure of patent ductus arteriosus (PDA in newborn infants born at 22–27 weeks gestational age (GA during pharmacological treatment with cyclooxygenase inhibitors. Method. Infants born at 22–27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory, and outcome parameters. Echocardiographic examinations during treatment were reviewed. Results. Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25+4 weeks versus 24+3 weeks; P=0.047, and a higher pretreatment left to right maximal ductal flow velocity (1.6 m/s versus 1.1 m/s; P=0.023. Correcting for GA, preeclampsia, antenatal steroids, and age at start of treatment, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04; P=0.049. Conclusion. Maximal ductal flow velocity was independently associated with success of PDA treatment.

  3. Mena invasive (Mena(INV)) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM.

    Science.gov (United States)

    Roussos, Evanthia T; Goswami, Sumanta; Balsamo, Michele; Wang, Yarong; Stobezki, Robert; Adler, Esther; Robinson, Brian D; Jones, Joan G; Gertler, Frank B; Condeelis, John S; Oktay, Maja H

    2011-08-01

    Mena, an actin regulatory protein, functions at the convergence of motility pathways that drive breast cancer cell invasion and migration in vivo. The tumor microenvironment spontaneously induces both increased expression of the Mena invasive (Mena(INV)) and decreased expression of Mena11a isoforms in invasive and migratory tumor cells. Tumor cells with this Mena expression pattern participate with macrophages in migration and intravasation in mouse mammary tumors in vivo. Consistent with these findings, anatomical sites containing tumor cells with high levels of Mena expression associated with perivascular macrophages were identified in human invasive ductal breast carcinomas and called TMEM. The number of TMEM sites positively correlated with the development of distant metastasis in humans. Here we demonstrate that mouse mammary tumors generated from EGFP-Mena(INV) expressing tumor cells are significantly less cohesive and have discontinuous cell-cell contacts compared to Mena11a xenografts. Using the mouse PyMT model we show that metastatic mammary tumors express 8.7 fold more total Mena and 7.5 fold more Mena(INV) mRNA than early non-metastatic ones. Furthermore, Mena(INV) expression in fine needle aspiration biopsy (FNA) samples of human invasive ductal carcinomas correlate with TMEM score while Mena11a does not. These results suggest that Mena(INV) is the isoform associated with breast cancer cell discohesion, invasion and intravasation in mice and in humans. They also imply that Mena(INV) expression and TMEM score measure related aspects of a common tumor cell dissemination mechanism and provide new insight into metastatic risk.

  4. Infiltrating Ductal Carcinoma Co-Existing with Intraductal Papillary Carcinoma of Male Breast: A Rare Case Report.

    Science.gov (United States)

    Kumar, Mayank; Pottipati, Bhaswanth; Arakeri, Surekha U; Javalgi, Anita P

    2017-06-01

    Male breast carcinomas are rare tumours, accounting for less than 1% of all malignancies in men. Intracystic Papillary Carcinoma (IPC) in males is a very rare entity, representing 5-7.5% of all male breast carcinomas. It lacks the classical clinical, radiological and cytological features of malignancy and usually presents as a benign-appearing lump. We report a case of Infiltrating Ductal Carcinoma (IDC) co-existing with intracystic papillary carcinoma in a 53-year-old male who presented with lump in the right breast.

  5. Correlation of MRI apparent diffusion coefficient of invasive breast cancer with tumor tissue growth and angiogenesis

    Directory of Open Access Journals (Sweden)

    Ze-Hong Fu

    2017-08-01

    Full Text Available Objective: To study the correlation of MRI apparent diffusion coefficient (ADC value of invasive breast cancer with tumor tissue growth and angiogenesis. Methods: Patients with breast mass who were treated in Wuhan No. 6 Hospital between March 2014 and May 2017 were selected as the research subjects and divided into group A with invasive ductal carcinoma, group B with intraductal carcinoma and group C with benign lesion according to the biopsy results, magnetic resonance diffusion-weighted imaging was conducted to determine ADC values, and biopsy tissue was taken to determine the expression of proliferation genes and angiogenesis genes. Results: USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A and group B were significantly higher than those of group C while ADC value as well as ALEX1 and Bax protein expression levels were significantly lower than those of group C; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in lesions of group A were significantly higher than those of group B while ADC value as well as ALEX1 and Bax protein expression levels was significantly lower than those of group B; USP39, CyclinD1, VEGF, bFGF, Angplt-2, Angplt-3 and Angplt-4 protein expression levels in invasive breast cancer tissue with high ADC value were significantly lower than those in invasive breast cancer tissue with low ADC value while ALEX1 and Bax protein expression levels were significantly higher than those in invasive breast cancer tissue with low ADC value. Conclusion: The decrease of ADC value of invasive breast cancer is closely related to cancer cell proliferation and angiogenesis.

  6. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

  7. Measurement of indicator genes using global complementary DNA (cDNA) amplification, by polyadenylic acid reverse transcriptase polymerase chain reaction (poly A RT-PCR): A feasibility study using paired samples from tissue and ductal juice in patients undergoing pancreatoduodenectomy.

    Science.gov (United States)

    Sanyal, Sudip; Siriwardena, Ajith K; Byers, Richard

    2018-06-01

    The aim of this study is to compare gene expression profiles in RNA isolated from pancreatic ductal juice with the RNA expression profiles of the same genes from matched intra-operative tissue samples from pancreatic tumours. Intra-operative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreatoduodenectomy for clinically suspected pancreatic cancer and a precursor lesion, main-duct intraductal papillary mucinous neoplasm. RNA was isolated and Poly A PCR was used to globally amplify the RNA. Real-time polymerase chain reaction (RT-PCR) was used to measure expression levels of 17 genes selected from microarray studies. Spearman's rank correlation test was used to examine the relationship of gene expression between pancreatic juice and tissue. The study was approved by Regional Ethics Committee. Mesothelin (MSLN) showed significant correlation (p cDNA using poly A PCR is technically feasible. Application of the technique to non-invasively obtained pancreatic juice during endoscopic assessment of tumours and the use of gene arrays of cancer indicator genes are the next steps in development of this technique. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Management of invasive species

    DEFF Research Database (Denmark)

    Schou, Jesper Sølver; Jensen, Frank

    impact of the establishment of this invasive species is a substantial increase in the number of allergy cases, which we use as a measure of the physical damage. As valuation methods, we use both the cost-of-illness method and the benefit transfer method to quantify the total gross benefits of the two...... policy actions. Based on the idea of an invasion function, we identify the total and average net benefit under both prevention and mitigation. For both policy actions, the total and average net benefits are significantly positive irrespective of the valuation method used; therefore, both prevention...... and mitigation are beneficial policy actions. However, the total and average net benefits under mitigation are larger than the benefits under prevention, implying that the former policy action is more beneficial. Despite this result, we conclude that prevention, not mitigation, shall be used because...

  9. SMAD4 Loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells

    International Nuclear Information System (INIS)

    Chen, Yu-Wen; Hsiao, Pi-Jung; Weng, Ching-Chieh; Kuo, Kung-Kai; Kuo, Tzu-Lei; Wu, Deng-Chyang; Hung, Wen-Chun; Cheng, Kuang-Hung

    2014-01-01

    SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully characterized. The AsPC-1, CFPAC-1 and PANC-1 human PDAC cell lines were used. The restoration or knockdown of SMAD4 expression in PDAC cells were confirmed by western blotting, luciferase reporter and immunofluorescence assays. In vitro cell proliferation, xenograft, wound healing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry analysis were conducted using PDAC cells in which SMAD4 was either overexpressed or knocked down. Here, we report that re-expression of SMAD4 in SMAD4-null PDAC cells does not affect tumor cell growth in vitro or in vivo, but significantly enhances cells migration in vitro. SMAD4 restoration transcriptionally activates the TGF-β1/Nestin pathway and induces expression of several transcriptional factors. In contrast, SMAD4 loss in PDAC leads to increased expression of E-cadherin, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and CD133. Furthermore, SMAD4 loss causes alterations to multiple kinase pathways (particularly the phosphorylated ERK/p38/Akt pathways), and increases chemoresistance in vitro. Finally, PDAC cells with intact SMAD4 are more sensitive to TGF-β1 inhibitor treatment to reduced cell migration; PDAC cells lacking SMAD4 showed decreased cell motility in response to EGFR inhibitor treatment. This study revealed the molecular basis for SMAD4-dependent differences in PDAC with the aim of identifying the subset of patients likely to respond to

  10. Prenyltransferase inhibitor radiosensitization of pancreatic ductal carcinoma (PaCa) cells

    International Nuclear Information System (INIS)

    Brunner, T.B.; Hahn, S.M.; Rustgi, A.K.

    2003-01-01

    Farnesyltransferase inhibitors (FTIs) radiosensitize tumor cell lines expressing activated H-Ras. K-Ras however remains active after FTI treatment due to prenylation by geranylgeranyltransferase. Up to 90% of pancreatic carcinomas (PaCa) are mutant in K-ras. We hypothesized that combined FTI and geranylgeranyltransferase inhibitor (GGTI) treatment could radiosensitize PaCa cells. Nine human PaCa lines (7 K-ras-mutant, 2 ras-wt) and transgenic mouse pancreatic ductal cells (PDC) expressing wt-ras or mutant K-ras were tested in clonogenic assays with combined FTI-A +/- GGTI-B (Merck and Co Inc.). Inhibition of PI3- kinase (with LY294002) or inhibition of MEK1/2 (with U0126) served to assess the significance of the PI3-kinase and MAPK to radiation survival in these cells. H- and K-Ras prenylation status and changes in phosphorylation of AKT and MAPK were monitored as were changes in cell cycle distribution. FTI+GGTI treatment achieved inhibition of K-Ras prenylation in all PaCa cell lines. This treatment radiosensitized the K-ras mutant cell lines AsPC-1, Capan-2, MiaPaCa-2 and PSN-1, PancM, but not Capan-1 or the ras-wt cell lines (BxPC-3, HS766T, PDC-wt). L-778,123, a dual action inhibitor, sensitized all K-ras mutant cells. Surprisingly, PancM, Panc-1, MiaPaCa-2 and PDC K-Ras cells were radiosensitized by FTI treatment alone. R11577, another FTI without GGTI activity, also sensitized Panc-1 and MiaPaCa-2 and additionally AsPC-1 cells. Radiosensitization was also achieved after treatment with LY294002 in all PaCa lines expressing mutant-K-ras and the ras-wt line BxPC-3 overexpressing Akt2. However these lines were not sensitized by U0126. FTI+GGTI sensitize K-ras mt PaCa cell lines to radiation. PI3-kinase signaling but not MAPK signaling appears to contribute to radiation survival in PaCa cells. Radiosensitization of certain PaCa cells by FTI alone indicates that alternate pathways or farnesylated targets other than K-Ras may also be involved in radiation survival

  11. Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hawthorn Lesleyann

    2010-08-01

    Full Text Available Abstract Background A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs. This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'. Methods We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs. Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH analysis to identify genes showing altered expression in LOH regions. Results Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples. Conclusion We have demonstrated the utility of the application of

  12. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma.

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    Huanwen Wu

    Full Text Available Epidermal growth factor receptor (EGFR is highly expressed in pancreatic ductal adenocarcinoma (PDAC and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.In the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.In total, 64 (48.9% patients expressed EGFR, 68 (51.9% expressed CXCR4, and 33 (25.2% coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938. EGFR expression significantly correlated with tumor differentiation (P = 0.031, whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001. EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026, TNM stage (P = 0.048, and poor tumor differentiation (P = 0.004. By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS and overall survival (OS. Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001 and OS (HR = 2.48, P = 0.001.In conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse

  13. SMAD4 loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells.

    Science.gov (United States)

    Chen, Yu-Wen; Hsiao, Pi-Jung; Weng, Ching-Chieh; Kuo, Kung-Kai; Kuo, Tzu-Lei; Wu, Deng-Chyang; Hung, Wen-Chun; Cheng, Kuang-Hung

    2014-03-14

    SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully characterized. The AsPC-1, CFPAC-1 and PANC-1 human PDAC cell lines were used. The restoration or knockdown of SMAD4 expression in PDAC cells were confirmed by western blotting, luciferase reporter and immunofluorescence assays. In vitro cell proliferation, xenograft, wound healing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry analysis were conducted using PDAC cells in which SMAD4 was either overexpressed or knocked down. Here, we report that re-expression of SMAD4 in SMAD4-null PDAC cells does not affect tumor cell growth in vitro or in vivo, but significantly enhances cells migration in vitro. SMAD4 restoration transcriptionally activates the TGF-β1/Nestin pathway and induces expression of several transcriptional factors. In contrast, SMAD4 loss in PDAC leads to increased expression of E-cadherin, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and CD133. Furthermore, SMAD4 loss causes alterations to multiple kinase pathways (particularly the phosphorylated ERK/p38/Akt pathways), and increases chemoresistance in vitro. Finally, PDAC cells with intact SMAD4 are more sensitive to TGF-β1 inhibitor treatment to reduced cell migration; PDAC cells lacking SMAD4 showed decreased cell motility in response to EGFR inhibitor treatment. This study revealed the molecular basis for SMAD4-dependent differences in PDAC with the aim of identifying the subset of patients likely to respond to

  14. Associations between ABO blood groups and pancreatic ductal adenocarcinoma: influence on resection status and survival.

    Science.gov (United States)

    El Jellas, Khadija; Hoem, Dag; Hagen, Kristin G; Kalvenes, May Britt; Aziz, Sura; Steine, Solrun J; Immervoll, Heike; Johansson, Stefan; Molven, Anders

    2017-07-01

    Both serology-based and genetic studies have reported an association between pancreatic cancer risk and ABO blood groups. We have investigated this relationship in a cohort of pancreatic cancer patients from Western Norway (n = 237) and two control materials (healthy blood donors, n = 379; unselected hospitalized patients, n = 6149). When comparing patient and blood donor ABO allele frequencies, we found only the A 1 allele to be associated with significantly higher risk for pancreatic ductal adenocarcinoma (PDAC) (23.8% vs. 17.9%; OR = 1.43, P = 0.018). Analyzing phenotypes, blood group A was more frequent among PDAC cases than blood donors (50.8% vs. 40.6%; OR = 1.51, P = 0.021), an enrichment fully explained by the A 1 subgroup. Blood group O frequency was lower in cases than in blood donors (33.8% vs. 42.7%; OR = 0.69, P = 0.039). This lower frequency was confirmed when cases were compared to hospitalized patients (33.8% vs. 42.9%; OR = 0.68, P = 0.012). Results for blood group B varied according to which control cohort was used for comparison. When patients were classified according to surgical treatment, the enrichment of blood group A was most prominent among unresected cases (54.0%), who also had the lowest prevalence of O (28.7%). There was a statistically significant better survival (P = 0.04) for blood group O cases than non-O cases among unresected but not among resected patients. Secretor status did not show an association with PDAC or survival. Our study demonstrates that pancreatic cancer risk is influenced by ABO status, in particular blood groups O and A 1 , and that this association may reflect also in tumor resectability and survival. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ

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    Davies Mary

    2008-06-01

    Full Text Available Abstract Background Debate regarding the benefit of radiotherapy after local excision of ductal carcinoma in situ (DCIS continues. The Van Nuys Prognostic Ind