WorldWideScience

Sample records for schirrous invasive ductal

  1. [Differential diagnosis of invasive ductal carcinoma versus invasive lobular carcinoma of breast].

    Science.gov (United States)

    Yin, Hong-Fang; Li, Ting; Zhang, Hong; Zhang, Shuang

    2009-10-01

    To study the diagnostic usefulness of immunohistochemical markers in distinguishing between invasive ductal carcinoma and invasive lobular carcinoma of breast. Twenty-four cases of grade I invasive ductal carcinoma, 12 cases of classic invasive lobular carcinoma and 14 cases of invasive carcinoma with mixed ductal and lobular features were retrieved from the archival files of Peking University First Hospital during the period from January, 1998 to December, 2001. Immunohistochemical study for E-cadherin, p120 catenin, epithelia membrane protein 1 (EMP1) and DVL1 was performed. The positivity rates for E-cadherin in grade I invasive ductal carcinoma and classic invasive lobular carcinoma were 83.3% (20/24) and 0, respectively (P invasive ductal carcinoma (membranous staining) and classic invasive lobular carcinoma (cytoplasmic staining). The positivity rates for EMP1 and DVL1 in gradeI invasive ductal carcinoma were 95.8% (23/24) and 54.2% (13/24), respectively; while those in classic invasive lobular carcinoma were 12 and 5 cases, respectively. E-cadherin and p120 catenin are useful immunomarkers for distinguishing between invasive ductal carcinoma and invasive lobular carcinoma. On the other hand, EMP1 and DVL1 are of limited value in this respect.

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

    Science.gov (United States)

    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.

  3. Comparison of the clinicopathological features of invasive ductal, invasive lobular, and mixed (invasive ductal + invasive lobular) carcinoma of the breast.

    Science.gov (United States)

    Zengel, Baha; Yararbas, Ulkem; Duran, Ali; Uslu, Adam; Elıyatkın, Nukhet; Demırkıran, Mehmet Ali; Cengiz, Fevzi; Şimşek, Cenk; Postacı, Hakan; Vardar, Enver; Durusoy, Raika

    2015-07-01

    In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated. A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach. The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %). MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  6. Invasive ductal carcinoma of the mammary gland in a mare.

    Science.gov (United States)

    Hirayama, K; Honda, Y; Sako, T; Okamoto, M; Tsunoda, N; Tagami, M; Taniyama, H

    2003-01-01

    A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.

  7. Comparison of enhancement characteristics between invasive lobular carcinoma and invasive ductal carcinoma.

    NARCIS (Netherlands)

    Mann, R.M.; Veltman, J.; Huisman, H.J.; Hitge-Boetes, C.

    2011-01-01

    PURPOSE: To compare enhancement characteristics between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) on contrast enhanced MRI of the breast and to observe the magnitude of eventual differences as these may impair the diagnostic value of breast MRI in ILC. MATERIALS AND

  8. Invasive ductal breast cancer metastatic to the sigmoid colon

    Directory of Open Access Journals (Sweden)

    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.

  9. Large mammary hamartoma with focal invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  10. Ki-67 marker useful for classification of malignant invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Irmawati Hassan

    2015-12-01

    The study showed that invasive ductal breast cancer with high Ki-67 index was significantly associated with high grade of malignacy. The high Ki-67 marker index can be used for classification of the grade of malignancy of invasive ductal breast cancer.

  11. 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......, and invasive carcinomas. Overlaps were, however, evident among the groups. There were no significant differences between means of the quantitative variables obtained in carcinoma in situ of the ductal and the lobular type with or without accompanying invasive carcinoma (2p > or = 0.22). A close correlation......, and the nuclear volume fraction, Vv(nuc/tis). The vv(nuc), aH(nuc), and MI were, on average, larger in ductal than in lobular carcinomas (2p carcinomas (2p = 3.10(-4). Comparing estimates obtained in tumors of pure ductal carcinoma in situ (N = 11) with those...

  12. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    Directory of Open Access Journals (Sweden)

    Fernando N. Aguiar

    2013-05-01

    Full Text Available OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1 and 146 samples associated with invasive carcinoma (group 2. Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER and progesterone receptor (PR status, human epidermal growth factor receptor 2 (HER2 expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2 and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease.

  13. Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications.

    Science.gov (United States)

    Barroso-Sousa, Romualdo; Metzger-Filho, Otto

    2016-07-01

    Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Science.gov (United States)

    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.

  16. 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

    lesions, and invasive carcinomas. Overlaps were, however, evident among the groups. There were no significant differences between means of the quantitative variables obtained in carcinoma in situ of the ductal and the lobular type with or without accompanying invasive carcinoma (2p > or = 0.22). A close...

  17. Invasive Ductal Carcinoma Arising in Phyllodes Tumor With Isolated Tumor Cells in Sentinel Lymph Node

    Directory of Open Access Journals (Sweden)

    Ying-Ju Kuo

    2010-11-01

    Full Text Available Phyllodes tumor (PT consists of stroma of variable grading and benign ductal epithelium. Although exceptional, carcinomas that arise from the epithelium in PTs do exist, and seem to behave less aggressively than the usually encountered breast carcinoma. To the best of our knowledge, among the invasive carcinomas that have arisen in PTs, only 1 has been proved to have metastatic carcinoma in the lymph nodes. Here, we describe the youngest woman to have invasive ductal carcinoma that arose in a borderline PT, with isolated carcinoma cells in the sentinel lymph node. Whether such a combined lesion carries a more indolent course is also discussed.

  18. The highly expressed COL4A1 genes contributes to the proliferation and migration of the invasive ductal carcinomas

    Science.gov (United States)

    Liu, Qiliang; Liao, Caihua; Ma, Hailin; Li, Sijing; Yu, Zhaoxia

    2017-01-01

    Background Invasive ductal carcinoma is a kind of very typical breast cancer. The goal of our research was to figure out the molecular mechanism of Invasive ductal carcinoma and to find out its potential therapy targets. Results The total amount of 478 differentially expressed genes in Invasive ductal carcinoma which compared with normal breast epithelial cells were recognized. Functional enrichment analysis proved the most part of differentially expressed genes had connection with ECM-receptor interaction. The two genes lists were contrasted in PPI network, and miRNA regulation networks, The most two crucial genes were identified in our study, which may be helpful to improve Invasive ductal carcinoma treatment. Additionally, experimental results shows that the COL4A1 gene, one of identified genes, played important roles in both of proliferation and colony formation in Invasive ductal carcinoma. Conclusions Invasive ductal carcinoma could have connection with ECM-receptor mutations. These 9 vital genes could be an important part in the progression of Invasive ductal carcinoma and be offered as therapy targets and prognosis indicator. and the experimental results showed that one of the most crucial genes, COL4A1, was the key gene that influence the proliferation and colony formation of the Invasive ductal carcinoma cell. PMID:28938546

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

    Science.gov (United States)

    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.

  20. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

    Science.gov (United States)

    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.

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

    Science.gov (United States)

    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 < 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

    Directory of Open Access Journals (Sweden)

    Neto Guerino

    2012-04-01

    Full Text Available Abstract This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.

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

    Science.gov (United States)

    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.

  5. Expression of sarcosine metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.

    Science.gov (United States)

    Cha, Yoon Jin; Jung, Woo Hee; Cho, Nam Hoon; Koo, Ja Seung

    2015-05-01

    The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results. Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)]. The sarcosine metabolic phenotype differed between ILC and IDC (plow sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC. Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.

  6. Expression of autophagy related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma.

    Science.gov (United States)

    Cha, Yoon Jin; Kim, Yon Hee; Cho, Nam Hoon; Koo, Ja Seung

    2014-01-01

    The aim of this study is to compare the expression of autophagy related proteins in invasive lobular carcinoma (ILC) with that of autophagy related proteins in invasive ductal carcinoma (IDC), and to determinate its implication. Tissue microarray containing 114 ILC and 692 IDC was constructed, and immunohistochemistry was performed for autophagy related protein (beclin-1, LC3A, LC3B, p62) and Ki-67. No significant difference in expression of autophagy-related proteins between pleomorphic type (n = 12) and classic type (n = 102) of ILC was observed, whereas ILC and IDC showed distinguished features that tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 were highly expressed in IDC and tumoral BNIP3 was highly expressed in ILC (P < 0.001). Beclin-1 expression was correlated with ER negativity (P = 0.016) and TNBC type (P = 0.024). BNIP3 expression was correlated with ER positivity (p = 0.040). Using multivariate Cox analysis, shorter overall survival was associated with tumoral beclin-1 positivity (hazard ratio: 21.19, 95% CI: 1.098-409.1, P = 0.043). In conclusion, ILC and IDC showed different expression pattern of autophagy-related proteins in tumor and stroma that demonstrated by higher expression of tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 in IDC, and higher expression of tumoral BNIP3 in ILC.

  7. The expression pattern of MUC1 (EMA) is related to tumour characteristics and clinical outcome of invasive ductal breast carcinoma

    NARCIS (Netherlands)

    van der Vegt, B.; Peterse, J. L.; Patriarca, C.; Hilkens, J.; de Bock, G. H.; Wesseling, J.; de Roos, M.A.J.

    Aims: To clarify MUC1 patterns in invasive ductal breast carcinoma and to relate them to clinicopathological parameters, coexpression of other biological markers and prognosis. Methods and results: Samples from 243 consecutive patients with primary ductal carcinoma were incorporated into tissue

  8. Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Lisa Leung

    Full Text Available Lipocalin 2 (LCN2 is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.

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

    Science.gov (United States)

    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.

  10. Pleomorphic Invasive Ductal Carcinoma of the Breast in a Patient with Huntington's Disease.

    Science.gov (United States)

    Shousha, Sami

    2014-01-01

    A pleomorphic invasive ductal carcinoma developed in a patient with Huntington's disease. The tumour showed marked nuclear pleomorphism and contained large number of bizarre tumour giant cells and abundant abnormal mitoses. Tumour cells showed nuclear vesicles and inclusions similar to those described in nuclei of neural cells in patients with Huntington's disease. The case suggests that, in some patients, tumour morphology may reflect specific individual features.

  11. Pleomorphic Invasive Ductal Carcinoma of the Breast in a Patient with Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Sami Shousha

    2014-01-01

    Full Text Available A pleomorphic invasive ductal carcinoma developed in a patient with Huntington’s disease. The tumour showed marked nuclear pleomorphism and contained large number of bizarre tumour giant cells and abundant abnormal mitoses. Tumour cells showed nuclear vesicles and inclusions similar to those described in nuclei of neural cells in patients with Huntington’s disease. The case suggests that, in some patients, tumour morphology may reflect specific individual features.

  12. Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas.

    Science.gov (United States)

    Liu, Qun; Li, Ji-guang; Zheng, Xin-yu; Jin, Feng; Dong, Hui-ting

    2009-11-20

    Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-like markers (CD133, paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. In 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins. CD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis. PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed. Detecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.

  13. Epitrochlear lymph node metastases from invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Kumar Pavan

    2009-01-01

    Full Text Available Metastasis to an epitrochlear lymph node from a primary invasive breast cancer has not been reported earlier. We report a case of epitrochlear lymph node metastasis that presented 10 years after the primary breast malignancy had been treated with radiotherapy, chemotherapy, and hormonal therapy. The patient was successfully treated and continues to remain asymptomatic more than 2 years after she presented with the metastasis.

  14. 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.

  15. Comparison of invasive micropapillary and triple negative invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Chen, Hong-liang; Ding, Ang

    2015-12-01

    Invasive micropapillary carcinoma (IMPC) of the breast and triple negative breast cancer (TNBC) are both aggressive subtypes, but little information is available on their comparison. Retrospective analysis of 95 IMPC and 200 TNBC-IDC (invasive ductal carcinoma) was conducted to compare the clinicopathologic characteristics and survivals. For IMPC, pN was the independent prognostic factor of local-regional recurrence free survival (LRRFS) (P = 0.045) and metastasis free survival (MFS) (P = 0.048), but not of overall survival (OS) (P = 0.165). For TNBC, pT and lymphovascular invasion (LVI) were both independent prognostic factors of MFS (pT: P = 0.006, LVI: P = 0.010) and OS (pT: P = 0.006, LVI: P = 0.001), but not for LRRFS (pT: P = 0.060, LVI: P = 0.503). IMPC exhibited more aggressive features than TNBC, including larger tumor size, a greater proportion of nodal involvement, and an increased incidence of LVI. After a median follow-up duration of 61 months, 5y-LRRFS rate was lower in IMPC than in TNBC, in entire cohort (71.4 ± 4.8% vs. 89.8 ± 2.2%, P < 0.001) and in node positive cases (64.2 ± 5.9% vs. 81.7 ± 4.4%, P = 0.048). A tendency of lower 5y-MFS rate was observed in TNBC compared with in IMPC, in node positive cases (63.8 ± 5.5% vs. 74.8 ± 5.5%, P = 0.053) and in node negative cases (80.1 ± 3.6% vs. 96.2 ± 3.8%, P = 0.052), but it did not reach significance. 5y-OS was similar between IMPC and TNBC (81.9 ± 4.7% vs. 79.8 ± 3.1%, P = 0.475). IMPC is featured with high rate of lymph node involvement which is strongly associated with high rate of LRR. TNBC is featured with high rate of early distant metastasis without increase of nodal metastases. The survival is still relatively poor even in node negative cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

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

    Science.gov (United States)

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

    2015-12-01

    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 invasive components (p = 0.044). The intratumoral metabolic heterogeneity of (18) F-FDG PET was the most important predictor of invasive components of DCIS. • Preoperative identification of invasion in DCIS is important for axillary nodal management • Higher SUV max and lower AUC-CSH from FDG PET may indicate invasive components of DCIS • Higher TNR and COV from BSGI may indicate invasive components of DCIS • Lower ADC min and higher ADC diff from DWI may indicate invasive components of DCIS • AUC-CSH, an index of metabolic heterogeneity, is an independent predictor for invasive components.

  18. Myiasis associated with an invasive ductal carcinoma of the left breast: case study

    Directory of Open Access Journals (Sweden)

    Felipe Tavares Rodrigues

    Full Text Available ABSTRACT Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.

  19. 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.)

  20. Relationship between MMP-11 Expression in Invasive Ductal Breast Carcinoma with its Clinicopathologic Parameters

    Directory of Open Access Journals (Sweden)

    Farshad Naghshvar

    2017-04-01

    Full Text Available Background: Breast cancer is one of the most common cancers in the world, particularly in Iran. There are many genomic and molecular factors that cause the occurrence of breast cancer. Many markers are associated with tumor invasiveness. Matrix metalloproteinase includes a family of zinc-dependent endopeptidases that degrade various components of the extracellular matrix and basement membrane. Matrix metalloproteinase expressions increase in thyroid, colorectal, head and neck squamous cell carcinoma, lung, and ovarian cancers. It is correlated with tumor angiogenesis, invasion, and metastasis. Matrix metalloproteinase 11 is a member of the stromelysin subclass of the matrix metalloproteinase family. This enzyme is secreted to become a potentially active form against other matrix metalloproteinases. Contradictory results exist regarding the correlation between matrix metalloproteinase 11 expression and clinicopathologic parameters in breast cancer. Methods: This case-control study examined 80 invasive ductal carcinoma of the breast and 80 adjacent nonneoplastic breast tissue paraffin blocks to identify the relationship between matrix metalloproteinase 11 expression and clinicopathologic parameters such as age, tumor size, microscopic grade, perineural and vascular invasion, lymph node involvement, and stage by immunohistochemistry analyses Results: Among the 80 patients, 86.3% showed matrix metalloproteinase 11 expression in tumor cells and 17.5% had matrix metalloproteinase 11 expression in adjacent normal breast tissue. This expression correlated with stage, grade, lymph node metastasis, and perineural and vascular invasion (P0.05. Conclusion: Matrix metalloproteinase 11 expression is increased in breast cancer and may be used as a predictive factor for tumor invasiveness.

  1. Multiphoton microscopic imaging of fibrotic focus in invasive ductal carcinoma of the breast

    Science.gov (United States)

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

    2014-11-01

    During the proliferation of breast cancer, the desmoplastic can evoke a fibrosis response by invading healthy tissue. Fibrotic focus (FF) in invasive ductal carcinoma (IDC) of the breast had been reported to be associated with significantly poorer survival rate than IDC without FF. As an important prognosis indicator, it's difficult to obtain the exact fibrotic information from traditional detection method such as mammography. Multiphoton imaging based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) has been recently employed for microscopic examination of unstained tissue. In this study, multiphoton microscopy (MPM) was used to image the fibrotic focus in invasive ductal carcinoma tissue. The morphology and distribution of collagen in fibrotic focus can be demonstrated by the SHG signal. Variation of collagen between IDC with and without FF will be examined and further characterized, which may be greatly related to the metastasis of breast cancer. Our result suggested that the MPM can be efficient in identifying and locating the fibrotic focus in IDC. Combining with the pathology analysis and other detecting methods, MPM owns potential in becoming an advanced histological tool for detecting the fibrotic focus in IDC and collecting prognosis information, which may guide the subsequent surgery option and therapy procedure for patients.

  2. Relationship between reticuloendothelial systems' FDG uptake level and clinicopathological features in patient with invasive ductal breast cancer.

    Science.gov (United States)

    Şahin, Ertan; Elboğa, Umut

    2017-10-01

    The reticuloendothelial system (RES) is a part of the immune system and plays a major role in the protection of against diseases. We thought that FDG-PET/CT may show the degree of systemic immune response induced with malignancy in the organs with the high RES activity. Our objective is to investigate FDG uptake levels of high RES activity organs (liver, spleen, bone marrow) in invasive ductal breast cancer and to evaluate the association with the clinicopathological features. In the present study, 193 patients with invasive ductal breast cancer who performed FDG-PET/CT were categorized according to the clinicopathological features including age, tumor size, axillary nodal status, histological grade, the presence of lymphavascular invasion, receptor status, Ki-67 proliferation index and biological subgroup. Also, a control group of 100 subjects were identified for comparison with breast cancer patients. We analyzed the relation of FDG uptake levels in high RES activity organs and clinicopathological features in patients. There was a statistically significant difference of SUVmax of the liver, spleen, and bone marrow between cancer and control groups (P features in patient with invasive ductal breast cancer. FDG uptake level in high RES activity organs is associated with the presence of tumor, and also directly relating clinicopathological features for patients with invasive ductal breast cancer.

  3. Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients

    NARCIS (Netherlands)

    Gregorowitsch, M.L. (M. L.); D.J. van den Bongard (Desirée); Young-Afat, D.A. (D. A.); J.-P. Pignol (Jean-Philippe); C.H. van Gils (Carla); May, A.M. (A. M.); H.M. Verkooijen (Helena)

    2017-01-01

    textabstractPurpose: Ductal carcinoma in situ (DCIS) is associated with an excellent prognosis; historical studies have shown similar levels of psychological distress in patients with DCIS and with early-stage invasive breast cancer (early-IBC). It is suggested that these results might have led to

  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 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 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 breast imaging is less likely to show all foci of ILC compared with IDC.

  5. Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features

    Science.gov (United States)

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

    2017-03-01

    Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 +/- 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.

  6. 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 Kepmean and SUVmax than ER or PR+ tumours. HER2- tumours displayed higher ADCmean, Kepmean, and SUVmax than HER2+tumours. Only ADCmean discriminated Ki67⩽14% tumours (lower ADCmean) 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.

  7. 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; Yang, Jin

    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.

  8. P08.23MULTIPLE CALCIFIED BRAIN METASTASES IN A MALE PATIENT WITH INVASIVE DUCTAL BREAST CANCER

    OpenAIRE

    Ressl, N.; Haindl, M.; Schenk, T.; Ungersboeck, K.; Sedivy, R.; Oberndorfer, S.

    2014-01-01

    Breast cancer in men is a rare disease and accounts for 1.6% of all malignancies of the breast. We report a case of a 51-year-old man with invasive ductal carcinoma of the breast with multiple calcified brain metastases. After modified radical mastectomy he received adjuvant chemotherapy with cyclophosphamide and doxorubicin, hormonal therapy and trastuzumab. About one year after initial diagnosis he developed a generalized epileptic seizure. Neuroradiological imaging (MRI) revealed multiple ...

  9. Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images

    OpenAIRE

    Roka Namoto Matsubayashi; Teruhiko Fujii; Kotaro Yasumori; Toru Muranaka; Seiya Momosaki

    2010-01-01

    Purpose. To investigate the correlation of Apperent Diffusion Coefficient (ADC) values in invasive ductal breast carcinomas with detailed histologic features and enhancement ratios on dynamic contrast-enhanced MRI. Methods and Materials. Dynamic MR images and diffusion-weighted images (DWIs) of invasive ductal breast carcinomas were reviewed in 25 (26 lesions) women. In each patient, DWI, T2WI, T1WI, and dynamic images were obtained. The ADC values of the 26 carcinomas were calculated with b-...

  10. [A Case of Invasive Ductal Carcinoma in the Fat Replacement of the Pancreatic Body and Tail].

    Science.gov (United States)

    Ebihara, Takeshi; Yamamoto, Tameyoshi; Hoshino, Hiromitsu; Yoshimura, Jumpei; Sasamatsu, Shingo; Hiraki, Yoko; Nishi, Hidemi; Shimizu, Katsushu; Kawada, Masahiro; Inoue, Toshiya; Kato, Fumitaka; Amano, Koji; Mikami, Jota; Yamamura, Jun; Makari, Yoichi; Nakata, Ken; Ikeda, Naoki; Kamigaki, Shunji; Tsujie, Masaki; Kimura, Yutaka; Nakata, Yasuki; Munakata, Satoru; Ohzato, Hiroki

    2015-11-01

    A 56 year-old woman with obesity (BMI3 2) and diabetes mellitus was diagnosed with right renal cell carcinoma. She underwent right nephrectomy 1 year ago. Seven months after surgery, CT revealed a rapidly growing mass near the spleen. The mass showed slight accumulation of FDG (SUVmax=2.4) on PET-CT. Since the lesion grew rapidly and was not enhanced in the early phase of enhanced CT, we diagnosed pancreatic cancer. Distal pancreatectomy and splenectomy were performed. The final pathological diagnosis was invasive ductal carcinoma in the fat replacement of the pancreatic body and tail. Postoperatively, the patient had no complications such as pancreatic fistula or aggravation of glucose intolerance. She received postoperative chemotherapy with gemcitabine. Since she developed pulmonary artery thrombosis, postoperative chemotherapy was interrupted after 8 courses. Thirty-two months after the surgery, she was still living without any recurrence. Acinar cells were absent in the fat replacement of the pancreas, but the pancreatic duct cells were still present. There was carcinoma in situ in the main pancreatic duct surrounding chronic inflammation. Fat replacement itself could be potentially precursor of the pancreatic cancer.

  11. Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and associated invasive carcinoma of the breast

    Science.gov (United States)

    Buerger, H; Simon, R; Schäfer, K-L; Diallo, R; Littmann, R; Poremba, C; van Diest, P J; Dockhorn-Dworniczak, B; Böcker, W

    2000-01-01

    Aims—The mutual relation of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive breast cancer, is controversial. Because they display genetic heterogeneity, it is not clear how genetically advanced these entities are and what causes the transition to an invasive carcinoma. Methods—Six cases of LCIS, four of them with associated lobular invasive carcinoma, four cases of intermediately differentiated DCIS with an associated invasive lobular carcinoma, and nine cases of intermediately and poorly differentiated DCIS with associated ductal invasive carcinoma were investigated by means of comparative genomic hybridisation (CGH) after microdissection and immunohistochemical staining of E-cadherin. Results—LCIS was characterised by a low average rate of copy number changes, no evidence of amplifications, and a high rate of gains and losses of chromosomal material at 1q and 16q, respectively. A high degree of genetic homology with well differentiated DCIS was obvious, as reported previously. The cases of intermediately differentiated DCIS with associated lobular invasive components and lobular differentiation revealed striking homologies, and a significant difference of E-cadherin expression. The comparison of preinvasive and invasive breast lesions, irrespective of differentiation within the same patient, revealed no specific alteration that might be associated with invasion. Genetic alterations seen in invasive carcinoma were not necessarily seen in the adjacent precursor lesions. Conclusions—These results provide strong evidence that invasive breast cancer is a disease with multiple cytogenetic subclones already present in preinvasive lesions. Moreover, specific CGH alterations associated with invasion were not observed. Furthermore, the close genetic association between well differentiated and a subgroup of intermediately differentiated DCIS and LCIS led to the hypothesis that LCIS and a

  12. Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ.

    Science.gov (United States)

    Mori, Kiyoshi; Takeda, Masashi; Kodama, Yoshinori; Kiyokawa, Hiroki; Yasojima, Hiroyuki; Mizutani, Makiko; Otani, Yoko; Morikawa, Nozomi; Masuda, Norikazu; Mano, Masayuki

    2017-06-01

    Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n=43) and pure DCIS (n=82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, "tumor thickness," extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor "thickness" was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. [Synchronous and ipsilateral invasive ductal carcinoma of the breast occurring near a phyllodes tumor - a case report].

    Science.gov (United States)

    Nagashima, Saki; Sakurai, Kenichi; Suzuki, Shuhei; Sakagami, Masashi; Enomoto, Katsuhisa; Amano, Sadao; Koshinaga, Tsugumichi

    2014-11-01

    We report 2 cases of invasive ductal carcinoma of the breast occurring near a phyllodes tumor. The first case was ofa 58- year-old woman who had a tumor in her right breast and visited our hospital. Following a core needle biopsy (CNB), a malignant phyllodes tumor was diagnosed. We performed a lumpectomy for the phyllodes tumor, with 1.5-cm surgical margins. Pathological diagnosis of the resected specimen confirmed the malignant phyllodes tumor. A ductal carcinoma in situ (DCIS) was also discovered near the phyllodes tumor. The second case was of another 58-year-old woman who had a big tumor in her right breast and visited our hospital. CNB resulted in pathological diagnosis ofa benign phyllodes tumor. The tumor was removed by a lumpectomy with 1.5-cm surgical margins. The pathological diagnosis from the resected specimen was borderline phyllodes tumor with invasive ductal carcinoma in the proximity. In both cases, DCIS could not have been diagnosed preoperatively.

  15. Salivary Duct Carcinoma and Invasive Ductal Carcinoma of the Breast: A Comparative Immunohistochemical Study.

    Science.gov (United States)

    Jalaly, Jalal B; Sanati, Souzan; Chernock, Rebecca D; Dibe, Dikson G; El-Mofty, Samir K

    2018-01-04

    Salivary duct carcinoma (SDC) is a high-grade salivary gland malignancy with great morphological resemblance to invasive ductal carcinoma (IDC) of the breast. Rarely, female patients may have a past history of both SDC and IDC. When these patients present with distant metastasis, accurate identification of the primary tumor is particularly difficult. Additionally, rare metastasis of SDC to the breast and IDC to the salivary (parotid) gland can also present a diagnostic challenge. Our aim was to develop an immunohistochemical panel that reliably distinguishes SDC from IDC. We included all SDCs diagnosed from 1989 to 2016 (23 cases) and 29 treatment naïve and histologically similar IDCs. All cases were stained with androgen receptor (AR), estrogen receptor-alpha (ER-α), progesterone receptor (PR), HER-2, CK5/6, p63, and beta-catenin. The great majority (> 90%) of both SDCs and IDCs reacted positively to AR. The main discrepancy in the immunohistochemical profiles was a distinctly different reactivity to ER-α, PR and HER-2. While 28 IDCs (96.6%) reacted positively to ER-α and/or PR, the majority expressing both (82.8%) with a moderate to strong staining intensity, only 2 SDCs expressed ER-α (8.7%) and 5 others expressed PR (21.7%) with only one case expressing both (P value SDC (34.8%) were positive for HER-2 while none of the IDCs were positive (P value SDC from IDC. Positive reactivity to ER-α, PR or both and negative HER-2 favors a diagnosis of IDC while ER-α, PR negative, HER-2 positive tumors are more likely SDC.

  16. 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.

  17. BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Min; Guo, Xiaojuan; Wang, Shuangkun [Capital Medical University, Department of Radiology, Beijing Chao Yang Hospital, Beijing (China); Jin, Mulan; Wang, Ying [Capital Medical University Beijing, Department of Pathology, Beijing Chaoyang Hospital, Beijing (China); Li, Jie; Liu, Jun [Capital Medical University Beijing, Department of Breast Surgery, Beijing Chaoyang Hospital, Beijing (China)

    2013-12-15

    To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma. A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1{alpha} (HIF-1{alpha}). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1{alpha} were respectively analysed. The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 {+-} 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1{alpha} (r = 0.516, P = 0.000). BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas. (orig.)

  18. Protein expression of c-erbB-2 and p53 in normal ducts, ductal carcinoma in situ and invasive carcinoma of the same breast

    Directory of Open Access Journals (Sweden)

    Marcus Vinicius Martins de Menezes

    Full Text Available CONTEXT AND OBJECTIVE: Breast cancer is thought to derive from progressively aberrant, non-invasive breast lesions, but it is not known exactly how invasive breast cancer develops from these lesions. The aim of this study was to verify the changes in c-erbB-2 and p53 protein expression between non-neoplastic ducts, ductal carcinoma in situ and invasive ductal carcinoma found in the same breast. DESIGN AND SETTING: This was a cross-sectional study at Centro de Atenção Integral à Saúde da Mulher, Campinas, Brazil. METHODS: Fifty-six women with invasive ductal carcinoma and ductal carcinoma in situ in the same breast were included. The expression of c-erbB-2 and p53 proteins was assessed in non-neoplastic and neoplastic cells using immunohistochemical techniques. RESULTS: The c-erbB-2 protein was absent in non-neoplastic ducts but was present in 46% and 36% of in situ and invasive carcinoma components, respectively. Only 2% of non-neoplastic ducts, and 18% and 16% of ductal carcinoma in situ and invasive carcinoma components, respectively, were positive for p53 protein. No significant difference in c-erbB-2 and p53 protein expression was observed between in situ and invasive components. The nuclear grade agreement between in situ and invasive carcinoma was very good. CONCLUSIONS: The invasiveness of ductal carcinoma in situ seems to be independent of the Her-2/neu and TP53 genes. The general features of an occurrence of breast carcinoma are formulated at the outset of carcinogenesis, and the Her-2/neu and TP53 genes are involved.

  19. Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal Breast Cancer: A Prospective Randomized Study.

    Science.gov (United States)

    Brück, N; Koskivuo, I; Boström, P; Saunavaara, J; Aaltonen, R; Parkkola, R

    2018-03-01

    Preoperative magnetic resonance imaging has become an important complementary imaging technique in patients with breast cancer, providing additional information for preoperative local staging. Magnetic resonance imaging is recommended selectively in lobular breast cancer and in patients with dense breast tissue in the case when mammography and ultrasound fail to fully evaluate the lesion, but the routine use of magnetic resonance imaging in all patients with invasive ductal carcinoma is controversial. The purpose of this randomized study was to investigate the diagnostic value of preoperative magnetic resonance imaging and its impact on short-term surgical outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. A total of 100 patients were randomized to either receive preoperative breast magnetic resonance imaging or to be scheduled directly to operation without magnetic resonance imaging on a 1:1 basis. There were 50 patients in both study arms. In 14 patients (28%), breast magnetic resonance imaging detected an additional finding and seven of them were found to be malignant. Six additional cancer foci were found in the ipsilateral breast and one in the contralateral breast. Magnetic resonance imaging findings caused a change in planned surgical management in 10 patients (20%). Mastectomy was performed in six patients (12%) in the magnetic resonance imaging group and in two patients (4%) in the control group ( p = 0.140). The breast reoperation rate was 14% in the magnetic resonance imaging group and 24% in the control group ( p = 0.202). The mean interval between referral and first surgical procedure was 34 days in the magnetic resonance imaging group and 21 days in the control group ( p magnetic resonance imaging may be beneficial for some patients with early-stage invasive ductal carcinoma, but its routine use is not recommended without specific indications.

  20. 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.

  1. Unusual Occurrence of Rare Lipid-Rich Carcinoma and Conventional Invasive Ductal Carcinoma in the One Breast: Case Report

    Directory of Open Access Journals (Sweden)

    Katarina Machalekova

    2012-01-01

    Full Text Available A 56-year-old woman noticed a palpable mass in her left breast during self-examination. Patient was admitted to our hospital and malignant bifocal tumour was diagnosed by ultrasonography, digital mammography, magnetic resonance, and core-cut biopsy. The patient underwent planned conservative surgery (biquadrantectomy with a sentinel node examination, but after results of the frozen section with positive resection margins and positive sentinel lymph nodes subsequent mastectomy with axillary lymph node dissection were realized. Histology in the resection specimen revealed two isolated and distinct tumours. One of the lesions represented conventional invasive ductal carcinoma of histological grade 3, and the second tumour was evaluated as invasive lipid-rich carcinoma, containing tumour cells with clear and foamy cytoplasm. Lipids in neoplastic cells were detected by Oil Red O staining and ultrastructural examination. Immunohistochemical analysis of both carcinomas was almost identical with negative steroid receptors, positive staining of HER-2, and p53 and with high proliferation activity (Ki-67. Mastectomy specimen contained residual foci of invasive ductal carcinoma and dissected axillary lymph nodes were free of metastasis. Patient underwent first cycles of chemotherapy with paclitaxel and Herceptin together with local radiotherapy and two month after surgery is without any evidence of the disease.

  2. Fibrotic focus: An important parameter for accurate prediction of a high level of tumor-associated macrophage infiltration in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Shimada, Hiroko; Hasebe, Takahiro; Sugiyama, Michiko; Shibasaki, Satomi; Sugitani, Ikuko; Ueda, Shigeto; Gotoh, Yoshiya; Yasuda, Masanori; Arai, Eiichi; Osaki, Akihiko; Saeki, Toshiaki

    2017-07-01

    Our group and others have previously reported that a fibrotic focus is a very useful histological factor for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 258 cases of invasive ductal carcinoma into those with and those without a fibrotic focus to investigate whether the presence of a fibrotic focus was significantly associated with the degree of tumor-associated macrophage (CD68, CD163 or CD204-positive) infiltration or whether the presence of tumor-associated macrophage infiltration heightened the malignant potential of invasive ductal carcinoma with a fibrotic focus. Multiple regression analyses demonstrated that a fibrotic focus was the only factor that was significantly associated with a high level of CD68-, CD163- or CD204-positive tumor-associated macrophage infiltration. The combined assessment of the presence or absence of a fibrotic focus and a high or a low level of CD204-positive tumor-associated macrophage infiltration clearly demonstrated that CD204-positive tumor-associated macrophage infiltration had a significant prognostic power only for patients with invasive ductal carcinoma with a fibrotic focus in multivariate analyses; CD204-positive tumor-associated macrophages might only exert a significant effect on tumor progression when a fibrotic focus is present within the invasive ductal carcinoma of the breast. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  3. Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.

    Science.gov (United States)

    Aquino, Ranniere Gurgel Furtado DE; Vasques, Paulo Henrique Diógenes; Cavalcante, Diane Isabelle Magno; Oliveira, Ayane Layne DE Sousa; Oliveira, Bruno Masato Kitagawa DE; Pinheiro, Luiz Gonzaga Porto

    2017-01-01

    to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma. this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases. the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and pmastectomia radical ou quadrantectomia com esvaziamento axilar, oriundos do Serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil. Os tumores foram submetidos a processamento histológico e, em seguida, foram determinados os graus histológico (GH), tubular (GT), nuclear (GN), índice mitótico (IM) pela classificação de Scarff-Bloom-Richadson, verificada a presença de invasão angiolinfática (IA) e mensurado o maior diâmetro do tumor (DT). Tais variáveis foram correlacionadas com a presença de metástases axilares. a média de idade das pacientes foi 56,81 anos

  4. 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.

  5. 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.

  6. Loss of types XV and XIX collagen precedes basement membrane invasion in ductal carcinoma of the female breast.

    Science.gov (United States)

    Amenta, Peter S; Hadad, Salim; Lee, Maria T; Barnard, Nicola; Li, Deqin; Myers, Jeanne C

    2003-03-01

    Ductal and lobular carcinomas comprise most malignancies of the female breast and the morbidity and mortality associated with breast cancer. During the progression from in situ to invasive stages, tumour cells penetrate the epithelial and vascular basement membranes (BM) to realize full metastatic potential. While the definition of these structures has primarily resulted from analysis of laminin and type IV collagen, characterization of newly discovered BM/BM zone (BMZ) proteins will further elucidate the interactions between tumour cells and the host stroma. We have studied the expression of two non-fibrillar BMZ collagens, the type XV proteoglycan and collagen XIX, in breast cancer where a linear, well-formed BM becomes fragmented and even lost in the progression of epithelial malignancy. In the normal breast, types XV and XIX were found in all BMZ: epithelial, muscle, neural, endothelial, and fat. In in situ lesions, these two collagens, and particularly type XV, were often absent from the BM/BMZ displaying a continuous or just focally disrupted type IV/laminin staining pattern. In contrast, infiltrating ductal carcinomas showed only rare traces of laminin and collagen IV reactivity adjacent to the glands and tumour nests, and similarly there was little if any evidence of types XV and XIX collagen. All four molecules were, however, detected in the interstitium associated with some of the invasive carcinomas. The data suggest that types XV and XIX collagen are lost early in the development of invasive tumours, prior to penetration and eventual dissolution of the epithelial BM. Disappearance of these proteins from the BM/BMZ may signal remodelling of the extracellular matrix to promote tumour cell infiltration. Copyright 2003 John Wiley & Sons, Ltd.

  7. Hypoxia induces oncogene yes-associated protein 1 nuclear translocation to promote pancreatic ductal adenocarcinoma invasion via epithelial-mesenchymal transition.

    Science.gov (United States)

    Wei, Honglong; Xu, Zongzhen; Liu, Feng; Wang, Fuhai; Wang, Xin; Sun, Xueying; Li, Jie

    2017-05-01

    Pancreatic ductal adenocarcinoma is one of the most lethal cancers. The Hippo pathway is involved in tumorigenesis and remodeling of tumor microenvironments. Hypoxia exists in the microenvironment of solid tumors, including pancreatic ductal adenocarcinoma and plays a vital role in tumor progression and metastasis. However, it remains unclear how hypoxia interacts with the Hippo pathway to regulate these events. In this study, expressions of yes-associated protein 1 and hypoxia-inducible factor-1α were found to be elevated in pancreatic ductal adenocarcinoma samples compared with those in matched adjacent non-tumor samples. Moreover, hypoxia-inducible factor-1α expression was positively correlated with yes-associated protein 1 level in pancreatic ductal adenocarcinoma tissues. The higher expression of nuclear yes-associated protein 1 was associated with poor histological grade and prognosis for pancreatic ductal adenocarcinoma patients. In vitro, yes-associated protein 1 was highly expressed in pancreatic ductal adenocarcinoma cells. Depletion of yes-associated protein 1 inhibited the invasion of pancreatic ductal adenocarcinoma cells via downregulation of Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-13, and upregulation of E-cadherin. In addition, hypoxia promoted the invasion of pancreatic ductal adenocarcinoma cells via regulating the targeted genes. Hypoxia also deactivated the Hippo pathway and induced yes-associated protein 1 nuclear translocation. Furthermore, depletion of yes-associated protein 1 or hypoxia-inducible factor-1α suppressed the invasion of pancreatic ductal adenocarcinoma cells under hypoxia. Mechanism studies showed that nuclear yes-associated protein 1 interacted with hypoxia-inducible factor-1α and activated Snail transcription to participate in epithelial-mesenchymal transition-mediated and matrix metalloproteinase-mediated remodeling of tumor microenvironments. Collectively, yes-associated protein 1 is an

  8. 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

  9. A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population.

    Science.gov (United States)

    Lim, Seung Taek; Yu, Jong Han; Park, Heung Kyu; Moon, Byung In; Ko, Byung Kyun; Suh, Young Jin

    2014-03-13

    To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma (ILC) patients compared to invasive ductal carcinoma (IDC) patients according to their molecular subtype. We compared the clinicopathological characteristics, breast cancer-specific survival (BCSS) and overall survival (OS) between patients with IDC (n = 14,547) and ILC (n = 528). The ILC presented with a larger tumor size, more advanced cancer stage, increased rate of hormonal receptor positivity, human epidermal growth factor 2 (HER2) negativity and mastectomy than the IDC. The ILC patients more frequently presented with the luminal A subtype, whereas the IDC patients more frequently presented with the luminal B, HER2-overexpression, or triple negative subtype. The BCSS and OS were not significantly different between the IDC and ILC for each molecular subtype. Similar to IDC patients, molecular subtype should be considered when determining the prognosis and treatment regimen for ILC patients.

  10. Invasive ductal carcinoma of the breast with large central acellular zones (ring carcinoma): imaging and clinical findings in eight cases.

    Science.gov (United States)

    Connors, Alissa M; Svensson, William E; Sinnett, H Dudley; Shousha, Sami

    2005-10-01

    To review the mammographic and ultrasound appearances in patients who have invasive ductal carcinoma with a central acellular zone (ring carcinoma), as this feature has been reported to be associated with a poorer outcome. Eight patients were identified with ring carcinomas. Two breast radiologists reviewed their mammograms and ultrasound images. Patient records were reviewed to assess outcome. All patients had lesions deep within the breast, adjacent to the chest wall, five lesions were incompletely visualised on mammography. The appearance was of a circumscribed or obscured mass, without microcalcification. Five patients had ultrasound demonstrating a solid well-circumscribed hypoechoic microlobulated lesion. In our series of patients who have a ring carcinoma of the breast, mammographic and ultrasound appearances were similar in all cases and lacked the typical features of malignancy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of); Zeon, Seok Kil [Dept. of Nuclear Medicine, Bundang Jesaeng General Hospital, Sungnam (Korea, Republic of); Kim, Su Jin [Dept. of Anesthesiology and Pain Medicine, Dongguk University, School of Medicine, Gyeongju (Korea, Republic of)

    2015-03-15

    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{sub max}) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV{sub 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{sub 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.

  12. Prognostic value of the PAI-1 4G/5G polymorphism in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Yagmurdur, M C; Atac, F B; Tutar, N U; Verdi, H; Isiklar, I; Ozdemir, B H; Ozbek, N; Karakayali, H; Haberal, M

    2008-01-01

    The study group was derived from the archive materials of 55 invasive ductal breast cancer (IDC) patients who had undergone breast-preserving surgery (partial mastectomy/ axillary dissection). All patients included in the study had clinically T(1)-2, N0-M0 invasive ductal carcinoma. Genomic DNA species were extracted from paraffin-embedded blocks, and plasminogen activator inhibitor type-1 (PAI-1) gene 4G/5G genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Patient demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. PAI-1 4G/5G genotype frequencies were 4G/4G (64%), 4G/5G (31%), and 5G/5G (5%) in the patient group. According to the results based on frequencies, the demographics were not different. Five-year local recurrence rate of 4G/5G patients was the lowest (2/17, 12%) (P = 0.02). Also five-year distant metastases ratio of 4G/5G patients was the highest (18%) (P = 0.01). Five- and 10-year disease-free survival rates for the 4G/4G, 4G/5G, and 5G/5G groups were 97% and 94%, 82% and 77%, and 100% and 94%, respectively (P = 0.004). The results of this study indicate that the 4G allele in the PAI 1 gene had a negative impact on local recurrence and disease-free survival of patients with clinical T(1)-2N0M0 IDC.

  13. A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer

    OpenAIRE

    Glover, J A; Hughes, C M; Cantwell, M M; Murray, L J

    2011-01-01

    Background: Epidemiological studies have suggested a protective effect of cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drugs in breast cancer risk and disease progression. We performed a systematic review to evaluate the frequency of COX-2 expression in normal breast epithelium, ductal carcinoma in situ of breast (DCIS), DCIS-adjoining invasive breast cancer, microinvasive carcinoma of the breast (MICB) and invasive breast cancer. Methods: Literature searches were carried o...

  14. MOC-31 exhibits superior reactivity compared with Ber-EP4 in invasive lobular and ductal carcinoma of the breast: a tissue microarray study.

    Science.gov (United States)

    Pai, Reetesh K; West, Robert B

    2009-05-01

    Distinguishing between reactive mesothelial proliferations and adenocarcinoma is often very difficult. Ancillary studies, in particular immunohistochemistry, are often critical in detecting malignant epithelial cells, especially in serous effusion specimens. MOC-31 and Ber-EP4 are antibodies which target the epithelial cell adhesion molecule (Ep-CAM, TACSTD1) expressed in epithelial cells, and both are useful in distinguishing metastatic adenocarcinoma from reactive mesothelial cells. However, the reactivity of MOC-31 and Ber-EP4 with breast carcinoma, one of the more common carcinomas involving serous effusions, has not been extensively studied. We analyzed the immunohistochemical expression of MOC-31 and Ber-EP4 using tissue microarrays containing invasive ductal carcinoma (191 cases), invasive lobular carcinoma (44 cases), and 102 other carcinoma types comprising primary carcinomas of lung, gynecologic tract, pancreas, colon, gastric, esophageal, prostate, head and neck, hepatic, and renal origin. For MOC-31, 184 of 191 (96%) invasive ductal carcinomas and 39 of 44 (89%) invasive lobular carcinomas exhibited diffuse positive staining. In contrast, for Ber-EP4, 121 of 183 (66%) invasive ductal carcinomas and 11 of 40 (27.5%) invasive lobular carcinomas exhibited diffuse positive staining. With the exception of 1 case of esophageal adenocarcinoma, all other adenocarcinomas (86 of 87 cases) exhibited diffuse staining with both Ber-EP4 and MOC-31. MOC-31 and Ber-EP4 exhibited identical staining with all other carcinoma types. Our findings indicate that MOC-31 is superior to Ber-EP4 in detecting both invasive lobular and ductal carcinoma of the breast.

  15. Coexistence of Granular Cell Tumor and Invasive Ductal Breast Cancer in Contralateral Breasts: A Case Report

    Directory of Open Access Journals (Sweden)

    Maurizio Di Bonito

    2014-07-01

    Full Text Available Granular cell tumor (GCT is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up.

  16. Expression of e-cadherin, n-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt

    Directory of Open Access Journals (Sweden)

    Hanan Mohamed Abd ElMoneim

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features. METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas. RESULTS: The expression of E-cadherin was decreased (negative or weak in 37.1% of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9% and 40.9% of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1%, positive node status (80.9%, poor Nottingham Prognostic Index (64.7%, and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8% and nuclear Snail (69.4%. CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.

  17. Integrated PET/MR mammography for quantitative analysis and correlation to prognostic factors of invasive ductal carcinoma.

    Science.gov (United States)

    Kong, Eunjung; Chun, Kyung Ah; Bae, Young Kyung; Cho, Ihn Ho

    2016-01-19

    We investigated the relationship between 18F-FDG PET parameters and apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DWI) in patients with invasive ductal carcinoma (IDC). In addition, the prognostic utility of PET/MR mammography parameters was compared with that of known histologic prognostic factors. Forty-six women aged 50.7 ± 10.5 years underwent a preoperative PET/MR mammography assessment using an integrated PET/MR scanner. T1w, T2w, DWI [b value = 50, 400, and 800 s/mm2], dynamic contrast enhancement sequences, and 18F-FDG PET imaging were performed. IDCs were assessed using SUVmax values and intratumoral heterogeneities (IH) from the 18F-FDG PET images and mean (ADCmean) and minimum ADC (ADCmin) values were measured using the DWI images. Relationships between the PET parameters and ADC values were evaluated. Furthermore, SUVmax and ADC values were compared with histologic factors, tumor size, nodal status, lymphovascular invasion, Ki-67 expression and triple negative breast cancer (TNBC). In total 46 IDCs (2.1-7.5 cm in size) were analyzed. SUVmax (p = 0.012) and elevated IH (p = 0.041) were negatively correlated with ADCmin, then TNBC (p = 0.013) and high Ki-67 expression (p = 0.002) were associated with higher SUVmax. IDC with lymphovascular invasion had low ADCmin values (p = 0.045). 18F-FDG PET metabolic parameters and ADCmin were negatively correlated. PET parameters and ADC values might reflect the expression of biological features of tumors and tumor invasiveness, respectively. Integrated PET/MR mammography seemed like to have potential of a one-stop method for evaluating and predicting the prognosis of IDC.

  18. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma

    NARCIS (Netherlands)

    Qi, Liqiang; Bart, Joost; Tan, Lu Ping; Platteel, Inge; van der Sluis, Tineke; Huitema, Sippie; Harms, Geert; Fu, Li; Hollema, Harry; van den Berg, Anke

    2009-01-01

    Background: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA

  19. Nogo-B receptor expression correlates negatively with malignancy grade and ki-67 antigen expression in invasive ductal breast carcinoma.

    Science.gov (United States)

    Pula, Bartosz; Olbromski, Mateusz; Owczarek, Tomasz; Ambicka, Aleksandra; Witkiewicz, Wojciech; Ugorski, Maciej; Rys, Janusz; Zabel, Maciej; Dziegiel, Piotr; Podhorska-Okolow, Marzena

    2014-09-01

    Nogo-B receptor (NgBR) has been shown to be involved in endothelial cell chemotaxis and morphogenesis. However, few studies analyzing its expression in cancer cells have been performed. We examined NgBR expression in 233 patients with invasive ductal breast carcinoma (IDC) and corresponding non-malignant breast tissues (NMBT) on mRNA (real-time polymerase chain reaction) and protein levels (immunohistochemistry; IHC and western-blot analysis). NgBR expression was found also analyzed in breast cancer cell lines of varying invasiveness. NgBR expression was increased in IDC compared to NMBT on the mRNA (p=0.0007) and protein level (p=0.018). NgBR expression decreased significantly with IDC malignancy grade and correlated negatively with the Ki-67 antigen expression (r=-0.18; p=0.0005). High NgBR mRNA expression was associated with estrogen receptor negativity (p=0.0023) and the triple-negative phenotype of the tumors (p=0.0129). NgBR may be involved in IDC development, however, its role in its progression requires further research. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Shear-wave elastography in invasive ductal carcinoma: correlation between quantitative maximum elasticity value and detailed pathological findings.

    Science.gov (United States)

    Cho, Eun Yoon; Ko, Eun Sook; Han, Boo-Kyung; Kim, Rock Bum; Cho, Sooyoun; Choi, Ji Soo; Hahn, Soo Yeon

    2016-05-01

    Further information is needed regarding whether histopathological characteristics affect breast tumor elasticity. To determine whether maximum elasticity values vary according to tumor-stroma ratio, dominant stroma type, or presence of fibrosis in invasive breast cancer. This study included 71 patients with invasive ductal carcinoma not otherwise specified (IDC NOS) who underwent breast shear-wave elastography (SWE). Maximum elasticity (Emax) values were retrospectively correlated with pathological findings that included tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with Emax. High histologic grade was significantly correlated with higher Emax (P = 0.042). Estrogen receptor and progesterone receptor expression negatively correlated with high elasticity values (P = 0.013 and P = 0.03, respectively). Breast cancers that exhibited higher cellularity demonstrated a greater level of stiffness that was not statistically significant (ρ = 0.153; P = 0.193). While dominant stroma type and fibrosis did not affect Emax (P = 0.197 and P = 0.598, respectively), lesion size was significantly associated with Emax (ρ = 0.474, P < 0.001). On multivariate analysis, only lesion size was significantly associated with Emax (P < 0.001). The composition of tumors did not affect their Emax. © The Foundation Acta Radiologica 2015.

  1. 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.

  2. Macroscopic lymphovascular invasion visualized on mammogram and magnetic resonance imaging: Initially misidentified as ductal carcinoma in situ but properly diagnosed by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Linda M Sanders

    2017-04-01

    Full Text Available Objectives: Lymphovascular invasion (LVI is a pathologic, microscopic finding associated with invasive cancer, and is a poor prognostic indicator, but has no reported imaging findings. This report presents the first documented case of LVI with seen by imaging. Linear branching microcalcifications were identified on mammography and clumped enhancement was noted on MRI, both imaging findings that are highly predictive of ductal carcinoma in situ (DCIS. Methods: Ultrasound guided core biopsy of the dominant mass was performed, confirming invasive ductal malignancy. Stereotactic biopsy performed on the microcalcifications was initially interpreted by pathology as DCIS. Results: Patient underwent mastectomy. Pathologic evaluation of the surgical specimen confirmed the invasive ductal malignancy. Microcalcifications were re-evaluated with immunohistochemistry (IHC and re-classified as LVI. Radiology images and IHC stains are shown. Conclusion: This is the first report of LVI identified by imaging with findings that mimicked DCIS and initially mis-identified as DCIS by pathology as well. The implications of this overlap in radiologic appearance are discussed.

  3. 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

  4. Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression.

    Science.gov (United States)

    El Deeb, Nevine M F; Mehanna, Radwa A

    2013-01-01

    Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters. Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor. Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104). Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.

  5. Paired ductal carcinoma in situ and invasive breast cancer lesions in the D-loop of the mitochondrial genome indicate a cancerization field effect.

    Science.gov (United States)

    Maggrah, Andrea; Robinson, Kerry; Creed, Jennifer; Wittock, Roy; Gehman, Ken; Gehman, Teresa; Brown, Helen; Harbottle, Andrew; Froberg, M Kent; Klein, Daniel; Reguly, Brian; Parr, Ryan

    2013-01-01

    Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM) from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1) in the D-loop portion of the mitochondrial genome (mtGenome) was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  6. Paired Ductal Carcinoma In Situ and Invasive Breast Cancer Lesions in the D-Loop of the Mitochondrial Genome Indicate a Cancerization Field Effect

    Directory of Open Access Journals (Sweden)

    Andrea Maggrah

    2013-01-01

    Full Text Available Alterations in the mitochondrial genome have been chronicled in most solid tumors, including breast cancer. The intent of this paper is to compare and document somatic mitochondrial D-loop mutations in paired samples of ductal carcinoma in situ (DCIS and invasive breast cancer (IBC indicating a potential breast ductal epithelial cancerization field effect. Paired samples of these histopathologies were laser-captured microdissected (LCM from biopsy, lumpectomy, and mastectomy tissues. Blood samples were collected as germplasm control references. For each patient, hypervariable region 1 (HV1 in the D-loop portion of the mitochondrial genome (mtGenome was sequenced for all 3 clinical samples. Specific parallel somatic heteroplasmic alterations between these histopathologies, particularly at sites 16189, 16223, 16224, 16270, and 16291, suggest the presence of an epithelial, mitochondrial cancerization field effect. These results indicate that further characterization of the mutational pathway of DCIS and IBC may help establish the invasive potential of DCIS. Moreover, this paper indicates that biofluids with low cellularity, such as nipple aspirate fluid and/or ductal lavage, warrant further investigation as early and minimally invasive detection mediums of a cancerization field effect within breast tissue.

  7. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    Science.gov (United States)

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  8. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  9. 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.

  10. 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.

  11. Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

    Science.gov (United States)

    Leonardi, Maria Cristina; Maisonneuve, Patrick; Mastropasqua, Mauro Giuseppe; Cattani, Federica; Fanetti, Giuseppe; Morra, Anna; Lazzari, Roberta; Bazzani, Federica; Caputo, Mariangela; Rotmensz, Nicole; Gerardi, Marianna Alessandra; Ricotti, Rosalinda; Enrica Galimberti, Viviana; Veronesi, Paolo; Dicuonzo, Samantha; Viale, Giuseppe; Jereczek-Fossa, Barbara Alicja; Orecchia, Roberto

    2017-09-01

    To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Predictors of invasive breast cancer and lymph node involvement in ductal carcinoma in situ initially diagnosed by vacuum-assisted breast biopsy: experience of 733 cases.

    Science.gov (United States)

    Trentin, Chiara; Dominelli, Valeria; Maisonneuve, Patrick; Menna, Simona; Bazolli, Barbara; Luini, Alberto; Cassano, Enrico

    2012-10-01

    To predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB). We retrospectively analyzed 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical-radiological variables with invasive component and nodal involvement. Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p 20 mm with nodal involvement, both highly significant. Older age, lesion <20 mm, and no residual lesion predict absence of invasion and no nodal involvement in VABB-diagnosed DCIS. However it would be imprudent to routinely forego sentinel node biopsy in such patients as non-negligible proportions of them have invasive disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up

    Energy Technology Data Exchange (ETDEWEB)

    Sztrokay, Aniko; Auweter, Sigrid D.; Liebhardt, Susanne; Hellerhoff, Karin; Reiser, Maximilian F. [Ludwig-Maximilians-Universitaet Muenchen, Department of Clinical Radiology, Munich (Germany); Herzen, Julia; Willner, Marian; Hahn, Dieter; Pfeiffer, Franz [Technische Universitaet Muenchen, Department of Physics, Garching (Germany); Mayr, Doris [Ludwig-Maximilians-Universitaet Muenchen, Institute of Pathology, Munich (Germany); Zanette, Irene [Technische Universitaet Muenchen, Department of Physics, Garching (Germany); European Synchrotron Radiation Facility (ESRF), Grenoble (France); Weitkamp, Timm [Synchrotron Soleil, L' Orme des Merisiers, Gif-sur-Yvette (France); Bamberg, Fabian [Ludwig-Maximilians-Universitaet Muenchen, Department of Clinical Radiology, Munich (Germany); LMU Munich, Institute of Clinical Radiology, Munich (Germany)

    2013-02-15

    Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS). Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion. Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS. Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS. (orig.)

  14. 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.

  15. 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.

  16. 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

    and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858......, 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...

  17. Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer

    Science.gov (United States)

    Liu, Ying; Pérez, Maria; Schootman, Mario; Aft, Rebecca L.; Gillanders, William E.; Jeffe, Donna B.

    2011-01-01

    Fear of cancer recurrence (FCR) is a common and persistent concern among breast cancer survivors. Little is known about factors associated with FCR in women with ductal carcinoma in situ (DCIS) or early invasive breast cancer (EIBC). Women with first primary DCIS, or stages I–IIA breast cancer were prospectively enrolled in a quality-of-life study and completed interviews at 4–6 weeks, 6 months, and 2 years after definitive surgical treatment. In three stepwise multivariable linear regression models, including both time-independent and time-varying variables measured at each respective interview, we identified independent correlates of mean FCR scores (range 1–6) using four items from the Concern About Recurrence Scale (CARS) at 2-year follow-up. Of 506 disease-free patients at 2-year follow-up (mean [SD] age, 58 [10] years; 81% White; 34% DCIS), the average FCR score of 2.0 was low. However, 145 (29%) reported moderate-to-high levels of FCR (scores 3.0–6.0). All three models showed that younger age, stage IIA breast cancer (vs. DCIS), lower social support, and elevated anxiety were consistently associated with higher FCR at 2-year follow-up (each P < 0.05; final models R2 = 0.25–0.32). DCIS patients reported lower FCR than stage IIA patients (each P ≤ 0.01) but had similar FCR as stage I patients. Although mean FCR was low, 29% of DCIS and EIBC survivors reported moderate-to-high levels of FCR at 2-year follow-up. Management of anxiety, provision of social support, and patient education may help reduce FCR among DCIS and EIBC survivors, especially among younger survivors. PMID:21553295

  18. Investigation of telomerase activity and apoptosis on invasive ductal carcinoma of the breast using immunohistochemical and Western blot methods.

    Science.gov (United States)

    Simsek, B C; Turk, B A; Ozen, F; Tuzcu, M; Kanter, M

    2015-08-01

    Invasive ductal carcinoma (IDC) comprises the largest group of breast cancers. This study aimed to investigate telomerase activity and apoptosis using immunohistochemical and Western blot methods. In total, 75 cases that had been diagnosed as IDC and 20 cases that had undergone a freezing procedure were included. The histological sections were stained with Bax, Bcl-2, hTERT and BNIP3. The ages of the patients, as well as their hormonal status and tumour sizes and grades were evaluated, as well as the staining characteristics of the antibodies in question. A decrease in Bcl-2 positivity and an increase in Bax positivity were found immunohistochemically with increasing tumour grades. The data obtained by western blot method showed that Bcl-2 was highest in grade 1 tumours although these results were not statistically significant. The relationship between estrogen and progesterone receptor positivity and Bcl-2 was statistically significant, suggesting there is hormonal control through apoptosis. BNIP3 was found to be decreased with increasing tumour grades. Similarly, BNIP3 was found to be having the lowest value in grade 3 tumours by western blot method. Furthermore, hTERT was found to be increased with increasing tumour grades. In the western blot method, hTERT increased nearly four-fold compared to the control. In addition, hTERT, which was seen in very high levels in tumours, may be a helpful cancer marker. Both hTERT and BNIP3 are important markers that can provide information about prognosis. Big improvements can be achieved in tumour progression control with new treatment modalities that stop telomerase activity and hypoxic cell death.

  19. Apparent diffusion coefficient in estrogen receptor-positive invasive ductal breast carcinoma: correlations with tumor-stroma ratio.

    Science.gov (United States)

    Ko, Eun Sook; Han, Boo-Kyung; Kim, Rock Bum; Cho, Eun Yoon; Ahn, Soomin; Nam, Seok Jin; Ko, Eun Young; Shin, Jung Hee; Hahn, Soo Yeon

    2014-04-01

    To determine whether apparent diffusion coefficient (ADC) values vary according to tumor-stroma ratio, dominant stroma type, or presence of central fibrosis in estrogen receptor-positive breast cancer. Institutional review board approval was obtained, and patient consent was waived. Sixty-one patients with estrogen receptor-positive invasive ductal carcinoma-not otherwise specified who underwent breast magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging were included in this study. The ADC values of the lesions were measured. Two pathologists evaluated the tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and central fibrosis. Detectability on DW images was compared between the two groups according to the tumor-stroma ratio (stroma rich or stroma poor). Mean ADC values were retrospectively compared with the tumor-stroma ratio, dominant stroma type, and presence of a central fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with ADC. On DW images, detectability was not significantly different between stroma-rich and stroma-poor groups (P = .244). ADC values were significantly lower in the stroma-poor group (P collagen-dominant type were lower than in fibroblast-dominant or lymphocyte-dominant types (P = .021). In multiple linear regression analysis, tumor-stroma ratio (P = .007), tumor size (P = .007), and dominant stroma type (collagen dominant, P = .029) were independently correlated with ADC. In estrogen receptor-positive breast cancers, ADC values showed significant differences according to the tumor-stroma ratio and dominant stroma type. RSNA, 2013

  20. Mast cells in invasive ductal breast cancer: different behavior in high and minimum hormone-receptive cancers.

    Science.gov (United States)

    della Rovere, Filippo; Granata, Angelo; Familiari, Dario; D'Arrigo, Graziella; Mondello, Baldassare; Basile, Giacomo

    2007-01-01

    Studies on the role of mast cells (MC) in cancer have given contrasting results. In order to contribute to the clarification of their role, research on breast cancer was carried out, because some aspects of its carcinogenesis, such as the diversity of the hormonal component, differ greatly. This study included 50 cases of invasive ductal breast cancer not otherwise specified (NOS): 25 of them were high hormone-receptive (HHR) cancers with estrogen and progesterone receptor values not lower than 50%, 25 were minimum hormone-receptive (MHR) cancers (< 5%). In both groups, mast cells were quantified in the peritumoral area. Twenty cases of surgical interventions for non-neoplastic esthetic prosthesis in healthy women were examined as controls. The proliferation index Ki-67 (MIB1) and the c-erb B2 receptor protein were also considered in cancer patients. Mast cells were detected using Giemsa and Alcian blue stains. The results obtained showed that there was a highly significant increase in the number of mast cells mainly in the peritumoral area in HHR cancer cases (p < 0.0001) compared to MHR cancers and controls (p < 0.0001). Comparison between mast cells in MHR cancer and control cases was not significant (p = 0.114). Hormone-receptive cancers have a less severe prognosis for their higher responsiveness to therapy. This element may suggest that the higher mast cell number present in these types of cancer is a favorable prognostic factor. Moreover, mast cells tend to accumulate around the cancer area and this can be seen as an attempt to oppose the progression of the anomalous tissue. Mast cells were reported to exhibit cytolytic activity against tumor cells.

  1. Associations between the standardized uptake value of (18)F-FDG PET/CT and the prognostic factors of invasive lobular carcinoma: in comparison with invasive ductal carcinoma.

    Science.gov (United States)

    Jung, Na Young; Kim, Sung Hun; Choi, Bo Bae; Kim, Sung Hoon; Sung, Mi Sook

    2015-03-15

    The aims of this study were to evaluate the associations between the maximum standardized uptake value (SUVmax) and prognostic factors in invasive lobular carcinoma (ILC) and to compare these results with those in invasive ductal carcinoma (IDC). The study included pathologically confirmed ILCs (n = 32) and IDCs (n = 73). We retrospectively evaluated the preoperative (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and measured the SUVmax. The pathologic results were reviewed regarding the size, histological type, histological grade, estrogen receptor (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and Ki-67 of the primary tumor. We also compared the associations between the SUVmax and prognostic factors. The mean SUVmax of the ILCs was significantly lower compared with that of the IDCs (P = 0.032). The SUVmax increased with tumor grade (P < 0.001) and was higher with ER negativity compared with ER positivity (P = 0.007) in IDC. The SUVmax was higher with EGFR positivity compared with EGFR negativity (P = 0.013) in IDC and higher with Ki-67 positivity compared with Ki-67 negativity in IDC and ILC (P < 0.001 and P = 0.002, respectively). The SUVmax was not significantly different regarding PR or HER2 for both tumor groups. The correlation between the tumor size and the SUVmax was demonstrated for IDCs (r = 0.57), but not for ILCs (r = 0.25). The SUVmax was significantly different according to the tumor grade, ER, EGFR, and Ki-67 for IDCs. The SUVmax exhibited a positive association with Ki-67 in ILC; however, it was not significantly different with other factors, which suggests that the role of (18)F-FDG PET/CT may be limited in ILC.

  2. Increased Breast Density Correlates with the Proliferation-Seeking Radiotracer 99mTc(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

    Directory of Open Access Journals (Sweden)

    Vassilios Papantoniou

    2011-09-01

    Full Text Available 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.

  3. 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

  4. Comparison of 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma.

    Science.gov (United States)

    Hogan, Molly P; Goldman, Debra A; Dashevsky, Brittany; Riedl, Christopher C; Gönen, Mithat; Osborne, Joseph R; Jochelson, Maxine; Hudis, Clifford; Morrow, Monica; Ulaner, Gary A

    2015-11-01

    Although guidelines such as those of the National Comprehensive Cancer Network consider (18)F-FDG PET/CT for systemic staging of newly diagnosed stage III breast cancer patients, factors in addition to stage may influence the utility of PET/CT. Because invasive lobular carcinoma (ILC) is less conspicuous than invasive ductal carcinoma (IDC) on (18)F-FDG PET, we hypothesized that tumor histology may be one such factor. We evaluated PET/CT systemic staging of patients newly diagnosed with ILC compared with IDC. In this Institutional Review Board-approved retrospective study, our Hospital Information System was screened for ILC patients who underwent PET/CT in 2006-2013 before systemic or radiation therapy. Initial stage was determined from examination, mammography, ultrasound, MR, or surgery. PET/CT was performed to identify unsuspected distant metastases. A sequential cohort of stage III IDC patients was evaluated for comparison. Upstaging rates were compared using the Pearson χ(2) test. The study criteria were fulfilled by 146 ILC patients. PET/CT revealed unsuspected distant metastases in 12 (8%): 0 of 8 with initial stage I, 2 of 50 (4%) stage II, and 10 of 88 (11%) stage III. Upstaging to IV by PET/CT was confirmed by biopsy in all cases. Three of 12 upstaged patients were upstaged only by the CT component of the PET/CT, as the metastases were not (18)F-FDG-avid. In the comparison stage III IDC cohort, 22% (20/89) of patients were upstaged to IV by PET/CT. All 20 demonstrated (18)F-FDG-avid metastases. The relative risk of PET/CT revealing unsuspected distant metastases in stage III IDC patients was 1.98 times (95% confidence interval, 0.98-3.98) that of stage III ILC patients (P = 0.049). For (18)F-FDG-avid metastases, the relative risk of PET/CT revealing unsuspected (18)F-FDG-avid distant metastases in stage III IDC patients was 2.82 times (95% confidence interval, 1.26-6.34) that of stage III ILC patients (P = 0.007). (18)F-FDG PET/CT was more likely to

  5. Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer.

    Science.gov (United States)

    Dobrescu, Andrei; Chang, Monique; Kirtani, Vatsala; Turi, George K; Hennawy, Randa; Hindenburg, Alexander A

    2011-01-01

    Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Apparent Diffusion Coefficient in Invasive Ductal Breast Carcinoma: Correlation with Detailed Histologic Features and the Enhancement Ratio on Dynamic Contrast-Enhanced MR Images

    Directory of Open Access Journals (Sweden)

    Roka Namoto Matsubayashi

    2010-01-01

    Full Text Available Purpose. To investigate the correlation of Apperent Diffusion Coefficient (ADC values in invasive ductal breast carcinomas with detailed histologic features and enhancement ratios on dynamic contrast-enhanced MRI. Methods and Materials. Dynamic MR images and diffusion-weighted images (DWIs of invasive ductal breast carcinomas were reviewed in 25 (26 lesions women. In each patient, DWI, T2WI, T1WI, and dynamic images were obtained. The ADC values of the 26 carcinomas were calculated with b-factors of 0 and 1000 s/mm2 using echoplanar DWI. Correlations of the ADC values were examined on dynamic MRI with enhancement ratios (early to delayed phase: E/D ratio and detailed histologic findings for each lesion, including cellular density, the size of cancer nests, and architectural features of the stroma (broad, narrow, and delicate between cancer nests. Results. The mean ADC was 0.915±0.151×10−3 mm2/sec. Cellular density was significantly correlated with ADC values (=.0184 and E/D ratios (=.0315. The ADC values were also significantly correlated to features of the stroma (broad to narrow, =.0366. Conclusion. The findings suggest that DWIs reflect the growth patterns of carcinomas, including cellular density and architectural features of the stroma, and E/D ratios may also be closely correlated to cellular density.

  8. Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy.

    Science.gov (United States)

    Catteau, Xavier; Simon, Philippe; Noël, Jean-Christophe

    2012-04-15

    15±30% of malignancies detected through screening programs are ductal carcinoma in situ (DCIS), and the majority of DCIS cases present in the form of mammographic microcalcification. This study was performed in order to determine the value of features in predicting invasive disease in patients with mammographic calcification and to help determine which patients (with, Core Needle Biopsy-diagnosed DCIS) are the most appropriate candidates for Sentinel Lymph Node (SLN) biopsy. The original aspect of this study was to select patients with mammographic microcalcification but without an associated mass. The factor that we identified to be associated with invasive disease at final surgical excision was the presence of necrosis at core histology. SLN biopsy or complete axillary lymph node dissection was performed in 22 (40%) patients of whom only one (4.5%) had a micrometastasis. Further larger studies are needed to see if it would be interesting to propose a SLN biopsy in case of necrosis on CNB-diagnosed DCIS with microcalcifications but not associated with a mass. Copyright © 2012 Elsevier GmbH. All rights reserved.

  9. Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis.

    Science.gov (United States)

    Charalampoudis, P; Agrogiannis, G; Kontzoglou, K; Kouraklis, G; Sotiropoulos, G C

    2017-08-01

    In breast cancer, hormonal receptors hold promise for developing novel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear. We studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters. TRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, or among different hormonal profiles and intrinsic subtypes. This is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  10. Inactivation of Brca2 cooperates with Trp53(R172H) to induce invasive pancreatic ductal adenocarcinomas in mice: a mouse model of familial pancreatic cancer.

    Science.gov (United States)

    Feldmann, Georg; Karikari, Collins; dal Molin, Marco; Duringer, Stephanie; Volkmann, Petra; Bartsch, Detlef K; Bisht, Savita; Koorstra, Jan-Bart; Brossart, Peter; Maitra, Anirban; Fendrich, Volker

    2011-06-01

    An inactivating germline mutation in BRCA2 is the most common known genetic basis for familial pancreatic cancer (FPC), accounting for 5-10% of inherited cases. A genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) arising on the backdrop of Brca2 deficiency is likely to elucidate valuable diagnostic and therapeutic insights for FPC. Both Brca2 alleles were conditionally deleted during development within the pancreatic epithelium by generating Pdx1-Cre; Brca2(f/f) (CB) mice; in addition, triple transgenic Pdx1-Cre; Brca2(f/f); LSL-Trp53(R172H) (CBP) mice were generated, in order to determine the impact of p53 deregulation on Brca2-deficient carcinogenesis. Both CB and CBP mice developed non-invasive ductal precursor lesions (murine pancreatic intraepithelial neoplasia or mPanIN), although these were observed at an earlier time point (5 versus 8 months) and with higher prevalence in CBP mice. A minority of CB mice (15%) developed invasive and metastatic PDAC at a latency of 15 months or greater; in contrast, CBP mice of comparable age uniformly developed PDAC with variable histological features. Mortality in the absence of neoplasia in CB and CBP mice was associated with profound loss of pancreatic parenchyma, consistent with progressive elimination of Brca2-deficient cells. Widespread DNA damage, as evidenced by overexpression of the phosphorylated histone H(2)AX(Ser139), was observed in the non-neoplastic exocrine pancreas, as well as in the mPanIN and PDAC lesions of Brca2-deficient mice, independent of p53 status. Loss of Brca2 function predisposes the exocrine pancreas to profound DNA damage, and the frequency of invasive neoplasia is accentuated by the concomitant deregulation of p53.

  11. Prediction of the presence of invasive disease from the measurement of extent of malignant microcalcification on mammography and ductal carcinoma in situ grade at core biopsy

    Energy Technology Data Exchange (ETDEWEB)

    O' Flynn, E.A.M. [South East London Breast Screening Programme and National Breast Screening Training Centre, Kings College Hospital NHS, London (United Kingdom)], E-mail: lizoflynn@doctors.org.uk; Morel, J.C. [South East London Breast Screening Programme and National Breast Screening Training Centre, Kings College Hospital NHS, London (United Kingdom); Gonzalez, J. [Department of Clinical Research Statistics, Kings College Hospital NHS Foundation Trust, London (United Kingdom); Dutt, N. [Department of Histopathology, Kings College Hospital NHS Foundation Trust, London (United Kingdom); Evans, D.; Wasan, R.; Michell, M.J. [South East London Breast Screening Programme and National Breast Screening Training Centre, Kings College Hospital NHS, London (United Kingdom)

    2009-02-15

    Aim: To determine whether the extent of microcalcification and ductal carcinoma in situ (DCIS) grade can be used to accurately predict the presence and size of invasive cancer in cases of malignant microcalcification. Materials and methods: Over a 10-year period, 402 cases of malignant microcalcification from an NHS screening programme were analysed. For each case, measurement of mammographic microcalcification extent, DCIS grade, and the presence and size of invasive carcinoma from the excised surgical specimen were recorded. Results: The final histological diagnosis was DCIS only in 71% (284/402) and DCIS with a focus of invasive disease in 29% (118/402). The risk of invasive disease increased with increasing size of microcalcification from 20% (27/136) for cluster size less than 11 mm, to 45% (18/40) for cluster size more than 60 mm. The risk of invasive disease also increased with increasing histological grade of DCIS from 13% (4/31) with low-grade DCIS to 36% (86/239) with high-grade DCIS. There were significant associations with the presence of invasive disease for cluster size (p = 0.0001) and DCIS grade (p = 0.003), and when using univariate analysis with simple [cluster size (p = 0.01) and grade (p = 0.01)] and multiple [cluster size (p = 0.02) and grade (p = 0.02)] logistic regression, respectively. The Hosmer-Lemeshow goodness-of-fit test suggests that the multiple logistic regression model has a good fit (p = 0.99). Conclusion: The multidisciplinary team can use these data in individual cases to estimate the risk of invasive cancer and decide whether to carry out an axillary staging procedure.

  12. 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.

  13. Ductal carcinoma in situ diagnosed at US-guided 14-gauge core-needle biopsy for breast mass: Preoperative predictors of invasive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ah Young; Gweon, Hye Mi; Son, Eun Ju; Yoo, Miri; Kim, Jeong-Ah; Youk, Ji Hyun, E-mail: jhyouk@yuhs.ac

    2014-04-15

    Objectives: To identify preoperative features that could be used to predict invasive breast cancer in women with a diagnosis of ductal carcinoma in situ (DCIS) at ultrasound (US)-guided 14-gauge core needle biopsy (CNB). Methods: A total of 86 DCIS lesions that were diagnosed at US-guided 14-gauge CNB and excised surgically in 84 women were assessed. We retrospectively reviewed the patients’ medical records, mammography, US, and MR imaging. We compared underestimation rates of DCIS for the collected clinical and radiologic variables and determined the preoperative predictive factors for upstaging to invasive cancer. Results: Twenty-seven (31.4%) of 86 DCIS lesions were upgraded to invasive cancer. Preoperative features that showed a significantly higher underestimation of DCIS were palpability or nipple discharge (p = 0.040), number of core specimens less than 5 (p = 0.011), mammographic maximum lesion size of 25 mm or larger (p = 0.022), mammographic mass size of 40 mm or larger (p = 0.046), sonographic mass size of 32 mm or larger (p = 0.009), lesion size of 30 mm on MR (p = 0.004), lower signal intensity (SI) on fat-saturated T2-weighted MR images (FS-T2WI) (p = 0.005), heterogeneous or rim enhancement on MR images (p = 0.009), and apparent diffusion coefficient (ADC) values lower than 1.04 × 10{sup −3} mm{sup 2}/s on diffusion-weighted MR imaging (DWI) (p < 0.001). Conclusion: Clinical symptom of palpability or nipple discharge, number of core specimen, mammographic maximum lesion or mass size, SI on FS-T2WI, heterogeneous or rim enhancement on MR, and ADC value may be helpful in predicting the upgrade to invasive breast cancer for DCIS diagnosed at US-guided 14-gauge CNB.

  14. Is there different correlation with prognostic factors between “non-mass” and “mass” type invasive ductal breast cancers?

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Lei, E-mail: jiang_belinder@sina.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Yiming, E-mail: zhou_belly@sina.com [Radiology Department, Chaoyang Hospital, Capital University, Baijiazhuang Road 8#, Chaoyang District, Beijing 100020 (China); Wang, Zheng, E-mail: wangzhengmay@163.com [Pathology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Lu, Xu, E-mail: luxu01@sina.cn [Surgery Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Chen, Min, E-mail: chenmin62@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China); Zhou, Cheng, E-mail: Chengzhou2000@yahoo.com [Radiology Department, Beijing Hospital, Peking University, The Ministry of Health, Dahua Road 1#, East District, Beijing 100730 (China)

    2013-09-15

    Purpose: To investigate the association between non-mass type breast cancer and common clinical–pathological prognostic factors, compared with mass type breast cancer. Materials and methods: After institutional review board approval, retrospective blind review of contrast-enhanced breast MRI was carried out for 88 histologically proven breast invasive ductal carcinoma (IDC) patients, presenting from January 2008 to December 2011. Two radiologists assessed the images of each lesion for the morphologic enhancement type [mass enhancement or non-mass-like enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two pathologists evaluated the histological grade of IDC, presence or absence of ductal carcinoma in situ (DCIS), lymph node status, presence or absence of vascular invasion, and expression status of estrogen receptor (ER)/progesterone receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer agreement was assessed with kappa test. Chi-square test and Spearman rank correlation were performed to explore the associations of morphologic enhancement type with the age, lesion size and the above pathological prognostic factors Results: Inter-observer agreement was excellent, with kappa > 0.75. Morphologic enhancement type was significantly correlated with age (P = 0.02), with NMLE more commonly seen in women less than 50 y/o. The size of NMLE was larger than that of mass and, with the increase of lesion size, proportion of NMLE among the cases increased (P = 0.001). NMLE was also significantly correlated with low histologic grade of IDC (P = 0.003) and presence of DCIS (P < 0.001). There was no significant correlation between morphologic enhancement type and lymph node status, vascular invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in clumped enhancement than non-clumped (P = 0.011). There was no correlation between enhancement distribution and prognostic factors Conclusions: Non-mass type breast cancer may

  15. Angiotensin II type 1 receptor (AT-1R) expression correlates with VEGF-A and VEGF-D expression in invasive ductal breast cancer.

    Science.gov (United States)

    Jethon, Aleksandra; Pula, Bartosz; Piotrowska, Aleksandra; Wojnar, Andrzej; Rys, Janusz; Dziegiel, Piotr; Podhorska-Okolow, Marzena

    2012-10-01

    Recent studies point to the involvement of angiotensin II (Ang II) receptor type 1 (AT-1R) on processes of metastasing, stimulation of invasiveness and angiogenesis in tumours. In this study, the correlation between intensity of AT-1R expression and expression of lymph- and angiogenesis markers in invasive ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced AT-1R expression. Expression intensity of AT-1R was found to correlate with expressions of VEGF-A (r = 0.26; p = 0.008) and VEGF-D (r = 0.24; p = 0.015). Out of the examined markers of angiogenesis and lymphangiogenesis only the pronounced expression of VEGF-C was found to correlate with patient poor clinical outcome (p = 0.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could point to stimulatory action of Ang II on their expression what might result in augmented lymph- and angiogenesis in IDC.

  16. 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.

  17. Detection of invasive components in cases of breast ductal carcinoma in situ on biopsy by using apparent diffusion coefficient MR parameters.

    Science.gov (United States)

    Mori, Naoko; Ota, Hideki; Mugikura, Shunji; Takasawa, Chiaki; Tominaga, Junya; Ishida, Takanori; Watanabe, Mika; Takase, Kei; Takahashi, Shoki

    2013-10-01

    To evaluate whether apparent diffusion coefficient (ADC) parameters could identify invasive components in cases with ductal carcinoma in situ (DCIS) diagnosed by biopsy. This retrospective study was approved by the institutional review board and the requirement to obtain informed consent was waived. Sixty-nine consecutive women with 70 lesions diagnosed with DCIS by biopsy underwent breast magnetic resonance (MR) imaging. Multiple regions of interest were placed (as many as possible) within the lesion on ADC maps. The minimum ADC values and the ADC difference values obtained as the difference between minimum and maximum ADCs were evaluated. Surgical specimens revealed 51 lesions with pure DCIS and the remaining 19 lesions with DCIS with invasive components (DCIS-IC). The minimum ADC value for DCIS-IC (0.99 ± 0.04 × 10(-3) mm(2)/s) was significantly lower than that of pure DCIS (1.15 ± 0.03 × 10(-3) mm(2)/s) (P  =  0.0037). The ADC difference value for DCIS-IC (0.38 ± 0.05 × 10(-3) mm(2)/s) was significantly higher than that of pure DCIS (0.17 ± 0.03 × 10(-3) mm(2)/s). ROC curve analysis for differentiating DCIS-IC from pure DCIS revealed that the area under the curve was 0.71 for minimum ADC value and 0.77 for ADC difference value. The minimum ADC values and ADC difference values could suggest the presence of invasive components. • Identification of invasive components in DCIS before treatment is clinically important. • Diffusion-weighted MR imaging can help lesion assessment in breast cancer. • The minimum ADC value may suggest the presence of an invasive component in DCIS. • The ADC difference value also suggests the presence of an invasive component in DCIS. • Preoperative evaluation of diffusion-weighted MR imaging may help surgical planning for DCIS.

  18. Histogram analysis of apparent diffusion coefficient at 3.0t: Correlation with prognostic factors and subtypes of invasive ductal carcinoma.

    Science.gov (United States)

    Kim, Eun Jeong; Kim, Sung Hun; Park, Ga Eun; Kang, Bong Joo; Song, Byung Joo; Kim, Yun Ju; Lee, Dongeon; Ahn, Hyunsoo; Kim, Inah; Son, Yo Han; Grimm, Robert

    2015-12-01

    To evaluate apparent diffusion coefficient (ADC) histogram parameters that show correlations with prognostic factors and subtypes of breast cancer. At 3.0T, various ADC histogram parameters were calculated including the entire tumor volume in 173 invasive ductal carcinomas: the minimum, 10th percentile, mean, median, 90th percentile, and maximum. ADC parameters were correlated with prognostic factors and subtype. The mean ADCmedian value was significantly higher in the group with lymph node metastasis, HER2 positivity, and a Ki-67 value correlation between ADCmedian and tumor size, histologic grade, estrogen receptor expression, and progesterone receptor expression (P = 0.272, 0.113, 0.261, and 0.181, respectively). For most ADC parameters except for ADCmin , the mean of variable ADC parameters of HER2-positive, luminal A, luminal B-HER2(+), triple-negative, and luminal B-HER2(-) diseases were arranged in descending order (1.175, 0.936, 0.863, 0.811, and 0.665 × 10(-3) mm(2) /s in ADCmedian , respectively) with statistical significant difference (P coefficient = -0.317). Various ADC parameters were correlated with prognostic factors and subtype, except for ADCmin . HER2 positivity showed high ADC values and high Ki-67 index revealed low ADC values. © 2015 Wiley Periodicals, Inc.

  19. 36 cases adenoid cystic carcinoma of the breast in China: Comparison with matched grade one invasive ductal carcinoma-not otherwise specified.

    Science.gov (United States)

    Wang, Shuling; Li, Weidong; Wang, Fang; Niu, Yun; Hao, Chunfang; Wang, Xu; He, Lihong; Tong, Zhongsheng

    2017-04-01

    The aim of this study was to investigate the clinicopathological characteristic of adenoid cystic carcinoma (ACC). The clininopathological features, along with relapse free survival(RFS) and overall survival(OS) of 36 patients with ACC were retrospectively investigated and compared with those of 108 grade 1 invasive ductal carcinoma not-otherwise-specified (G1-IDC-NOS) patients. Most cases of ACC were ER, PR and HER-2 negative which was classified as triple-negative subtype. Five cases were concomitant with other pathological types of cancer. Axillary lymph node dissection(ALND) was performed in 31 patients and 2 of them with lymph nodes metastasis. Two patients died of lung metastases at 46 and 116 months after the surgery respectively. Compared with G1-IDC-NOS, ACC showed lower Ki-67 index, less lymph nodes metastasis, lower P53 expression, and higher proportion in location of upper outer quadrant of breast. There was no difference of OS and RFS between ACC and G1-IDC-NOS. ACC of the breast was a rare disease with a good prognosis although most of them were classified as triple-negative subtype. And the value of axillary node dissection and adjuvant therapy needs to be further investigated. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. High Frequency of Codon 12 but not Codon 13 and 61 K-ras Gene Mutations in Invasive Ductal Carcinoma of Breast in a South Indian Population.

    Science.gov (United States)

    Sushma, C; Prasad, Shiva; Devi, Rudrama; Murthy, Sudha; Rao, Ts; Naidu, Ck

    2015-01-01

    Ras genes are thought to play an important role in human cancer since they have been found to be activated frequently in several types of tumors including breast cancer, where the overall incidence of K-RAS oncogene activation is 0-10%. Evaluation of K-RAS gene not only for mutational frequency but also for mutation types in this downstream signaling gene pathway is necessary to determine the mechanisms of action. The present study was conducted to test the hypothesis that K-RAS activation is involved in breast cancer risk of south Indian population. A total of 70 paired pathologically confirmed tumor and non-tumor tissues from the same breast cancer patients were analysed for most common K-RAS mutations of codon 12,13 and 61 by polymerase chain reaction followed by restriction digestion and direct nucleotide sequencing method. We found that a high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in this study. Our study indicated that only codon 12 may be involved in initiating breast carcinogenesis in India.

  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

    tumor. These studies indicate that many of the epigenetic changes observed in invasive mammary cancer cells are clustered in the motility pathways that...including the essential roles that macrophages play in the micro- environments inwhichmammary tumor cells invade,migrate, and intravasate (5, 7). In...cancer cells located at the micro- anatomical sites of cancer cell intravasation, called TMEM (tumor micro- environment of metastasis) sites (22, 23

  2. Factors associated with {sup 18}F-fluorodeoxyglucose uptake in T1 and T2 invasive ductal carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, So Jung; Kim, Seong Jang; Kim, In Joo; Park, Kyoung June; Kim, Bum Soo; Shin, Seung Hyeon [Pusan National University Hospital, Pusan National University, Busan (Korea, Republic of)

    2016-09-15

    The objective of this study was to investigate the relationship between diversity of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake of primary tumor in positron emission tomography (PET) and various clinicopathologic factors in breast cancer of same pathologic T1, T2 stage. A total of 258 patients with invasive ductal breast cancer were enrolled in this study. All patients underwent {sup 18}F-FDG PET-CT before surgery. Patients were divided into two groups according to tumor size based on the pathologic T stage, and maximum standardized uptake value (SUV{sub max}) of 2.5, respectively. On the univariate analysis, estrogen receptor (ER), tumor size, lymphovascular invasion, p53, pathologic N status (pN) and Nottingham tumor grade (NG) were associated with high SUV{sub max} in T1 and T2 breast cancer. On the multivariate logistic regression, tumor size and NG remained significant variables dividing high and low SUV{sub max}. In the T1 group, ER, p53 and NG were significantly associated with high SUV{sub max} on the univariate analysis. In this group, p53 and NG remained significant variables for dividing high and low SUV{sub max} on the multivariate logistic regression. In the T2 group, only NG was associated with high SUV{sub max} on the univariate analysis.NG showed an association with {sup 18}F-FDG uptake in both T1 and T2 breast cancer independently; however, p53 in T1 breast cancer.

  3. 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

  4. Genetic clonal mapping of in situ and invasive ductal carcinoma indicates the field cancerization phenomenon in the breast.

    Science.gov (United States)

    Foschini, Maria P; Morandi, Luca; Leonardi, Elisa; Flamminio, Federica; Ishikawa, Yuko; Masetti, Riccardo; Eusebi, Vincenzo

    2013-07-01

    Nearly 80% of well-differentiated in situ duct carcinomas (g1 DCIS) have been shown to be multicentric (multilobar) lesions, while most in situ poorly differentiated duct carcinomas (g3 DCIS) were unifocal (unilobar) lesions. Here we present a clonality study of 15 cases of DCIS, all showing multiple foci. Twelve of these cases were associated with an invasive duct carcinoma. Fifteen cases of female breast cancer patients all showing multiple DCIS foci (5 g1 DCIS, 5 g2 DCIS, 5 g3 DCIS) were randomly selected and histologically studied using large histological sections. Care was taken to laser-microdissect DCIS foci that were most distantly located from one another in the same large section, and pertinent cells were genetically studied. Invasive duct carcinoma and ipsilateral lymph node metastases and/or contralateral lesions, whenever present, were additionally microdissected. DNA of neoplastic cells was purified, and the mtDNA D-loop region was sequenced. Genetic distance of different foci from the same case was visualized by phylogenetic analyses using the neighbor-joining method. Patients ranged in age from 36 to 87 years (mean 65.1). All 9 cases of widely spread DCIS were not clonal. Four of 6 cases that showed multiple adjacent foci were clonally related on mtDNA analysis. In the present series, 11/15 DCIS appeared as multiple synchronous primary breast tumors, genetically not related to one another. The present data enhance the view that breast can also show the field cancerization phenomenon, paralleling what has already been proposed in other organs. Copyright © 2013 Elsevier Inc. All rights reserved.

  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. Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.

    Science.gov (United States)

    Wang, Depu; Fu, Ling; Shah, Walayat; Zhang, Jingwen; Yan, Yan; Ge, Xinhong; He, Jianjun; Wang, Yili; Li, Xu

    2016-12-01

    The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH). One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC). HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731). HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. 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.

  8. Differences in Prognostic Factors and Failure Patterns Between Invasive Micropapillary Carcinoma and Carcinoma With Micropapillary Component Versus Invasive Ductal Carcinoma of the Breast: Retrospective Multicenter Case-Control Study (KROG 13-06).

    Science.gov (United States)

    Yu, Jeong Il; Choi, Doo Ho; Huh, Seung Jae; Cho, Eun Yoon; Kim, Kyubo; Chie, Eui Kyu; Ha, Sung W; Park, In Ae; Ahn, Sung Ja; Lee, Ji Shin; Shin, Kyung Hwan; Kwon, Youngmee; Kim, Yong Bae; Suh, Chang-Ok; Koo, Ja Seung; Kim, Jin Hee; Jeong, Bae Gwon; Kim, In Ah; Lee, Jong Hoon; Park, Won

    2015-10-01

    We designed the present study to investigate differences in prognostic factors and failure patterns between patients with invasive micropapillary carcinoma or carcinoma with micropapillary component (IMPC) and randomly matched patients with invasive ductal carcinoma (IDC) of the breast at multiple institutions of the Korean Radiation Oncology Group (KROG). This retrospective multicenter study was performed using subjects treated from January 1999 to November 2011. Female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy were considered for this study. Exact matches were made for age (± 3 years), pathologic tumor and node stage, treatment method (surgery with or without radiotherapy), and period when surgery was performed (within 1 year) at the same institution. A total of 534 patients were analyzed. The median follow-up period was 59 months in both groups. In the comparison of clinicopathologic characteristics, rates of lymphovascular invasion (LVI) and nuclear grade III were both significantly higher in IMPC than in IDC (P < .001, P = .01, respectively). During the follow-up period, recurrences developed in 40 patients with IMPC (15.0%) and 21 with IDC (7.9%). Locoregional recurrence (LRR) developed in 22 patients with IMPC (8.2%) and 10 with IDC (3.7%). The rate of distant metastasis did not differ between the 2 groups (P = .52). LRR-free survival (P = .03) and recurrence-free survival (P = .007) were significantly different between the 2 groups, but overall survival was not (P = .67). IMPC is associated with a higher rate of LVI, high nuclear grade, and a propensity for LRR compared to IDC. Modification of the locoregional treatment modality might be needed in this pathologic subtype of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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

  10. 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.

  11. Underestimation of invasive lesions in patients with ductal carcinoma in situ of the breast diagnosed by ultrasound-guided biopsy: A comparison between patients with and without HER2/neu overexpression

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Wei-Chou [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Hsu, Hsian-He, E-mail: hsianhe@yahoo.com.tw [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Yu, Jyh-Cherng [Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Ko, Kai-Hsiung [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Peng, Yi-Jen [Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Tung, Ho-Jui [Department of Healthcare Administration, Asia University, Taichung, Taiwan, ROC (China); Chang, Tsun-Hou; Hsu, Giu-Cheng [Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China)

    2014-06-15

    Purpose: To determine the rate of underestimation of ductal carcinoma in situ (DCIS) diagnosed at imaging-guided biopsy and to analyze its association with HER2/neu oncogene, an important biomarker in assessing the tumour aggressiveness and guiding hormone therapy for breast cancer. Methods: We retrospectively reviewed 162 patients with DCIS diagnosed by imaging-guided core needle biopsy between January 2008 and March 2013. All of these patients received surgical excision, and in 25, the diagnosis was upgraded to invasive breast cancer. In this study, we examined the ultrasound, mammographic features and histopathological results for each patient, and compared these parameters between those with and without HER2/neu overexpression. Results: Of the 162 DCIS lesions, 110 (67.9%) overexpressed HER2/neu. Nineteen patients with HER2/neu overexpressing DCIS (n = 19/110, 17.3%) were upgraded after surgery to a diagnosis of invasive breast cancer. In this group, the upgrade rate was highest in patients with a dilated mammary duct pattern (42.1%, n = 8/19, p = 0.02) and the presence of abnormal axillary nodes (40.0%, n = 12/30, p < 0.01) at ultrasound and was significantly associated with comedo tumour type on pathology. Conclusions: Biopsy may underestimate the invasive component in DCIS patients. Sonographic findings of dilated mammary ducts and presence of abnormal axillary lymph nodes may help predicting the invasive components and possibly driving more targeted biopsy procedures.

  12. Predictive factors for invasive cancer in surgical specimens following an initial diagnosis of ductal carcinoma in situ after stereotactic vacuum-assisted breast biopsy in microcalcification-only lesions.

    Science.gov (United States)

    Gümüş, Hatice; Mills, Philippa; Fish, David; Gümüş, Metehan; Cox, Karina; Devalia, Haresh; Jones, Sue; Jones, Peter; Sever, Ali R

    2016-01-01

    The aim of this study was to determine the incidence of invasive breast carcinoma in patients with preoperative diagnosis of ductal carcinoma in situ (DCIS) by stereotactic vacuum-assisted biopsy (SVAB) performed for microcalcification-only lesions, and to identify the predictive factors of invasion. From 2000 to 2010, the records of 353 DCIS patients presenting with microcalcification-only lesions who underwent SVAB were retrospectively reviewed. The mammographic size of microcalcification cluster, presence of microinvasion within the cores, the total number of calcium specks, and the number of calcium specks within the retrieved core biopsy specimen were recorded. Patients were grouped as those with or without invasion in the final pathologic report, and variables were compared between the two groups. The median age was 58 years (range, 34-88 years). At histopathologic examination of the surgical specimen, 63 of 353 patients (17.8%) were found to have an invasive component, although SVAB cores had only shown DCIS preoperatively. The rate of underestimation was significantly higher in patients with microcalcification covering an area of 40 mm or more, in the presence of microinvasion at biopsy, and in cases where less than 40% of the calcium specks were removed from the lesion. Invasion might be underestimated in DCIS cases diagnosed with SVAB performed for microcalcification-only lesions, especially when the mammographic size of calcification is equal to or more than 40 mm or if microinvasion is found within the biopsy specimen and less than 40% of the calcifications are removed. At least 40% of microcalcification specks should be removed from the lesion to decrease the rate of underestimation with SVAB.

  13. 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, o...

  14. Lack of CD151/integrin α3β1 complex is predictive of poor outcome in node-negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular and ductal breast cancers.

    Science.gov (United States)

    Romanska, Hanna M; Potemski, Piotr; Krakowska, Magdalena; Mieszkowska, Magdalena; Chaudhri, Shalini; Kordek, Radzisław; Kubiak, Robert; Speirs, Valerie; Hanby, Andrew M; Sadej, Rafał; Berditchevski, Fedor

    2015-11-03

    The proposed involvement of CD151 in breast cancer (BCa) progression is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and invasive lobular carcinoma (ILC) represent distinct disease entities. Here we evaluated clinical significance of CD151 alone and in association with integrin α3β1 in patients with ILC in context of the data of our recent IDC study. Expression of CD151 and/or integrin α3β1 was evaluated in ILC samples (N=117) using immunohistochemistry. The findings were analysed in relation to our results from an IDC cohort (N=182) demonstrating a prognostic value of an expression of CD151/integrin α3β1 complex in patients with HER2-negative tumours. Unlike in the IDCs, neither CD151 nor CD151/α3β1 complex showed any correlation with any of the ILC characteristics. Lack of both CD151 and α3β1 was significantly correlated with poor survival (P=0.034) in lymph node-negative ILC N(-) cases. The CD151(-)/α3β1(-) patients had 3.12-fold higher risk of death from BCa in comparison with the rest of the ILC N(-) patients. Biological role of CD151/α3β1 varies between ILC and IDC. Assessment of CD151/α3β1 might help to identify ILC N(-) patients with increased risk of distant metastases.

  15. Preoperative MRT of the breast in invasive lobular carcinoma in comparison with invasive ductal carcinoma; Praeoperative MRT der Brust beim invasiv-lobulaeren im Vergleich zum invasiv-duktalen Karzinom

    Energy Technology Data Exchange (ETDEWEB)

    Diekmann, F.; Diekmann, S.; Beljavskaja, M.; Taupitz, M.; Hamm, B. [Inst. fuer Radiologie, Universitaetsklinikum Charite, Berlin (Germany); Bick, U. [Inst. fuer Radiologie, Universitaetsklinikum Charite, Berlin (Germany); Dept. of Radiology, The Univ. of Chicago (United States); Blohmer, J.U. [Klinik und Poliklinik fuer Gynaekologie und Geburtshilfe, Universitaetsklinikum Charite, Berlin (Germany); Winzer, K.J. [Brustzentrum, Universitaetsklinikum Charite, Berlin (Germany)

    2004-04-01

    Purpose: To evaluate the role of preoperative MRI of the breast in invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC). Materials and Methods: For one year, all patients transferred by the hospital's gynecologic outpatient service for suspicious findings in routine mammography and/or ultrasound (conventional modalities=CM) underwent preoperative MRI of the breast. Retrospective analysis of the histologic findings identified 17 patients with ILC. These were compared with 30 proven IDC patients, chosen by random. The MRI findings of these 2 patient groups were compared with regard to the detection of additional lesions. The average number of additional lesions detected by MRI was compared for significant differences between both groups using the T-test for paired samples. Results: In the 17 patients with ILC, conventional modalities (CM) identified 21 malignant lesions whereas MRI detected a total of 30 lesions. At least one additional lesion was detected by MRI in 7 of the 17 patients with ILC. In the 30 patients with IDC, on the other hand, MRI detected an additional lesion in three instances only. In one patient of the ILC group, MRI identified an additional lesion in the contralateral breast that had escaped detection by CM. No additional contralateral lesion was detected by MRI in any of the IDC patients. Benefit of MRI in ILC-Group: The mean numbers of detected malignant lesions differed significantly between diagnosis by MRI and CM in the ILC group (1.77 carcinomas per patient with MRI versus 1.24 with conventional modalities, T-test, p=0.0078). Benefit of MRI in IDC-Group: although it was possible to find 1.27 carcinomas vs. 1.17 carcinomas per patient in the IDC-Group, this benefit was not statistical significant (T-test, p=0.0831). Conclusion: Preoperative MRI detects multiple additional lesions compared to the ones already known by CM. The higher incidence of multiple lesions in ILC compared to IDC and the difficult diagnosis

  16. Lacrimal gland ductal carcinomas

    DEFF Research Database (Denmark)

    Andreasen, Simon; Grauslund, Morten; Heegaard, Steffen

    2017-01-01

    PURPOSE: Ductal carcinomas (DCs) of the lacrimal gland are very rare but aggressive malignancies. We investigated DC of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options. METHODS: Case 1: A 77-year-old man, presented with diplopia...... 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...

  17. 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.)

  18. Squamoid eccrine ductal carcinoma: A diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Jayashree Krishnamurthy

    2014-01-01

    Full Text Available Squamoid eccrine ductal carcinoma (SEDC is a rare primary cutaneous tumor that exhibits both squamous and adnexal ductal differentiation. We report a case of SEDC presenting as multiple nodules on the scalp of a 58-year-old man. Histopathological examination of the excised lesion showed a tumor in the dermis composed of duct-like structures that represented the eccrine component and squamoid cells in nests and in an infiltrating pattern. Immunohistochemical (IHC positivity for cytokeratin 5/6, epithelial membrane antigen (EMA, and p63 confirmed the squamoid, ductal, and primary cutaneous nature, respectively, and differentiated it from eccrine poroma, microcystic adnexal carcinoma, and porocarcinoma with squamous differentiation. With a demonstrated invasive potential, recurrent nature, and ambiguous metastatic potential, Mohs micrographic surgery, an established and successful, yet tissue-sparing surgical modality with lower recurrence rate, is the recommended treatment of choice and a close follow-up of these patients is suggested for further experiences of this tumor.

  19. Immunohistochemical categorisation of ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    Meijnen, P.; Peterse, J. L.; Antonini, N.; Rutgers, E. J. Th; van de Vijver, M. J.

    2008-01-01

    The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma.

  20. Expression and Possible Prognostic Role of MAGE-A4, NY-ESO-1, and HER-2 Antigens in Women with Relapsing Invasive Ductal Beast Cancer: Retrospective Immunohistochemical Study

    Science.gov (United States)

    Bandić, Daniela; Juretić, Antonio; Šarčević, Božena; Šeparović, Viktor; Kujundžić Tiljak, Mirjana; Hudolin, Tvrtko; Spagnoli, Giulio C.; Čović, Dinko; Šamija, Mirko

    2006-01-01

    Aim To evaluate the possible prognostic role of the expression of MAGE-A4 and NY-ESO-1 cancer/testis antigens in women diagnosed with invasive ductal breast cancer and determine the expression of HER-2 antigen. Methods The expression of MAGE-A4, NY-ESO-1, and HER-2 antigens was evaluated immunohistochemically on archival paraffin-embedded samples of breast cancer tissue from 81 patients. All patients had T1 to T3, N0 to N1, M0 tumors and underwent postoperative radiotherapy and, if indicated, systemic therapy (chemotherapy and hormonal therapy). The antigen expression in women who were disease-free for 5 years of follow up (n = 23) was compared with that in women with either locoregional relapse (n = 30) or bone metastases (n = 28). Patient survival after 10 years of follow up was assessed. Results The three groups of women were comparable in terms of age, type of operation, tumor size, tumor grade, number of metastatically involved axillary lymph nodes, Nottingham prognostic index (NPI), progesterone receptor (PR) status, and adjuvant hormonal therapy. Estrogen receptors (ER) were positive in 13 women in the 5-year relapse-free group vs 8 in locoregional relapse and 7 in bone metastases group (P = 0.032). There were significantly fewer women who received adjuvant chemotherapy in the 5-year relapse-free group than in other two groups (7 vs 23 with locoregional relapse and 25 with bone metastases; P<0.001). This group also had a significantly better 10-year survival (14 women vs 1 with locoregional relapse and 1 with bone metastases; P<0.001). The three groups did not differ in the NY-ESO-1 or HER-2 expression, but the number of patients expressing MAGE-A4 antigen was significantly lower in the group with locoregional relapse (P = 0.014). In all groups, MAGE-A4 antigen expression was associated with the NY-ESO-1 antigen expression (P = 0.006), but not with tumor size and grade, number of metastatically involved axillary lymph nodes, or the ER

  1. Expression and possible prognostic role of MAGE-A4, NY-ESO-1, and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study.

    Science.gov (United States)

    Bandić, Daniela; Juretić, Antonio; Sarcević, Bozena; Separović, Viktor; Kujundzić-Tiljak, Mirjana; Hudolin, Tvrtko; Spagnoli, Giulio C; Cović, Dinko; Samija, Mirko

    2006-02-01

    To evaluate the possible prognostic role of the expression of MAGE-A4 and NY-ESO-1 cancer/testis antigens in women diagnosed with invasive ductal breast cancer and determine the expression of HER-2 antigen. The expression of MAGE-A4, NY-ESO-1, and HER-2 antigens was evaluated immunohistochemically on archival paraffin-embedded samples of breast cancer tissue from 81 patients. All patients had T1 to T3, N0 to N1, M0 tumors and underwent postoperative radiotherapy and, if indicated, systemic therapy (chemotherapy and hormonal therapy). The antigen expression in women who were disease-free for 5 years of follow up (n=23) was compared with that in women with either locoregional relapse (n=30) or bone metastases (n=28). Patient survival after 10 years of follow up was assessed. The three groups of women were comparable in terms of age, type of operation, tumor size, tumor grade, number of metastatically involved axillary lymph nodes, Nottingham prognostic index (NPI), progesterone receptor (PR) status, and adjuvant hormonal therapy. Estrogen receptors (ER) were positive in 13 women in the 5-year relapse-free group vs 8 in locoregional relapse and 7 in bone metastases group (P=0.032). There were significantly fewer women who received adjuvant chemotherapy in the 5-year relapse-free group than in other two groups (7 vs 23 with locoregional relapse and 25 with bone metastases; P<0.001). This group also had a significantly better 10-year survival (14 women vs 1 with locoregional relapse and 1 with bone metastases; P<0.001). The three groups did not differ in the NY-ESO-1 or HER-2 expression, but the number of patients expressing MAGE-A4 antigen was significantly lower in the group with locoregional relapse (P=0.014). In all groups, MAGE-A4 antigen expression was associated with the NY-ESO-1 antigen expression (P=0.006), but not with tumor size and grade, number of metastatically involved axillary lymph nodes, or the ER and PR status. MAGE-A4-positive patients had a

  2. Prognostic value of primary tumor SUVmax on F-18 FDG PET/CT compared with semi-quantitative tumor uptake on Tc-99m sestamibi breast-specific gamma imaging in invasive ductal breast cancer.

    Science.gov (United States)

    Yoo, Jang; Yoon, Hai-Jeon; Kim, Bom Sahn

    2017-01-01

    This study aimed to evaluate the prognostic value of F-18 FDG PET/CT in comparison with Tc-99m sestamibi breast-specific gamma imaging (BSGI) and previously established clinical prognostic parameters of invasive ductal breast carcinoma (IDC). We retrospectively included 157 female IDC patients (mean age 49.2 years, range 29.9-78.9) who underwent PET/CT and BSGI. The maximum standardized uptake value (SUVmax) and tumor to normal background ratios (TNRs) of their primary tumors were measured on PET/CT and BSGI, respectively. Univariate and multivariate survival analyses were performed to evaluate the prognostic value of the measured parameters and other clinical prognostic factors: age, menopausal status, breast density, pathologic tumor size (pTS), axillary nodal status (ANS), nuclear grade, histologic grade, hormone receptor status of estrogen (ER) and progesterone receptors (PR) and HER-2 expression. Among 157 patients, recurrences occurred in 22 patients (14.0 %). In univariate analyses, pTS (p < 0.0001), ANS (p < 0.0001), nuclear grade (p = 0.0046), histologic grade (p = 0.0001), ER status (p < 0.0001), PR status (p = 0.0037), HER-2 status (p = 0.0007), primary tumor SUVmax (p < 0.0001) and TNR (p = 0.0001) were significant predictors of recurrence. Among them, pTS (p = 0.0172), ANS (p = 0.0416), ER status (p = 0.0375) and primary tumor SUVmax (p = 0.0239) were independent prognostic factors in multivariate regression analysis. High primary tumor SUVmax of PET/CT and high TNR of BSGI were poor prognostic factors in IDC patients; in addition, primary tumor SUVmax was an independent prognostic factor along with pTS, ANS and ER status.

  3. 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}.

  4. 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.

  5. Ductal Carcinoma In Situ of the Breast

    Directory of Open Access Journals (Sweden)

    Richard J. Lee

    2012-01-01

    Full Text Available Ductal carcinoma in situ (DCIS of the breast represents a complex, heterogeneous pathologic condition in which malignant epithelial cells are confined within the ducts of the breast without evidence of invasion. The increased use of screening mammography has led to a significant shift in the diagnosis of DCIS, accounting for approximately 27% of all newly diagnosed cases of breast cancer in 2011, with an overall increase in incidence. As the incidence of DCIS increases, the treatment options continue to evolve. Consistent pathologic evaluation is crucial in optimizing treatment recommendations. Surgical treatment options include breast-conserving surgery (BCS and mastectomy. Postoperative radiation therapy in combination with breast-conserving surgery is considered the standard of care with demonstrated decrease in local recurrence with the addition of radiation therapy. The role of endocrine therapy is currently being evaluated. The optimization of diagnostic imaging, treatment with regard to pathological risk assessment, and the role of partial breast irradiation continue to evolve.

  6. Ductal carcinoma in situ: a challenging disease

    Directory of Open Access Journals (Sweden)

    Sevilay Altintas

    2011-12-01

    Full Text Available Ductal carcinoma in situ (DCIS represents a heterogenous group of lesions with variable malignant potential. Although it is clearly pre-invasive, not all lesions progress to an invasive malignant disease. The significant increase in the frequency of diagnosis is the result of both widespread use of screening mammography and better recognition among pathologists. Treatment is controversial, but for several decades total mastectomy has been considered as the appropriate treatment. The tendency to be less aggressive in terms of surgery has followed the pattern of events observed in the treatment of invasive breast carcinomas. More recently, it has become clear that breastconserving procedures could be applied and selected on the basis of diagnostics and risk factors. When all patients with DCIS are considered, the overall mortality is extremely low, only about 1–2%. On the other hand, breast-conserving surgery is only curative in 75–85%; 50% of the local recurrences have proven to be invasive with a mortality rate of 12–15%. There is no place for axillary node dissection, adjuvant hormonal treatment or chemotherapy in the treatment. Important factors in predicting local recurrence are age, family history, nuclear grade, comedo-type necrosis, tumor size and margin width. With the addition of radiation therapy to excisional surgery, there is a 50% reduction in the overall local recurrence rate. The Van Nuys Prognostic Index (VNPI, recently updated, is a tool that quantifies measurable prognostic factors that can be used in the decision-making process of treatment. Recent data from large cohort studies and randomized trials have emerged to guide treatment. DCIS is now understood to have diverse malignant potential and it is unlikely that there will be a single treatment for this wide range of lesions. Advances in molecular biology and gene expression profiling of human breast tumors have been providing important insights into the relationship

  7. 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

  8. 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.

  9. Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia

    Science.gov (United States)

    Prévot, Pierre-Paul; Simion, Alexandru; Grimont, Adrien; Colletti, Marta; Khalaileh, Abed; Van den Steen, Géraldine; Sempoux, Christine; Xu, Xiaobo; Roelants, Véronique; Hald, Jacob; Bertrand, Luc; Heimberg, Harry; Konieczny, Stephen F.; Dor, Yuval; Lemaigre, Frédéric P.; Jacquemin, Patrick

    2014-01-01

    Objective Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia (PanIN) and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). Transcriptional regulators required to initiate ADM still remain unknown, yet need to be identified to characterise the regulatory networks that drive ADM. Here we investigate the role of the ductal transcription factors Hepatocyte Nuclear Factor 6 (HNF6, also known as Onecut1)and SRY-related HMG box factor 9 (Sox9) in ADM. Design Expression of HNF6 and Sox9 is measured by immunostaining in normal and diseased human pancreas. The function of the factors is tested in cultured cells and in mouse models of ADM by a combination of gain- and loss-of-function experiments. Results Expression of HNF6 and Sox9 is ectopically induced in acinar cells in human ADM, as well as in mouse models of ADM. We show that these factors are required for repression of acinar genes, for modulation of ADM-associated changes in cell polarity, and for activation of ductal genes in metaplastic acinar cells. Conclusions HNF6 and Sox9 are new biomarkers of ADM and constitute candidate targets for preventive therapy in cases when ADM may lead to cancer. Our work also highlights that ectopic activation of transcription factors may underlie metaplastic processes occurring in other organs. PMID:22271799

  10. Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

    Directory of Open Access Journals (Sweden)

    Fernando Nalesso Aguiar

    2013-03-01

    Full Text Available PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS associated with adjacent invasive breast carcinoma (IBC. We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER, progesterone receptor (PR, human epidermal growth factor receptor 2 (HER2, cytokeratin 5/6 (CK5/6, and epidermal growth factor receptor (EGFR in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative, triple-positive (RE/RP/HER2-positive, HER2-enriched (ER/PR-negative/HER2-positive, and triple-negative (RE/RP/HER2-negative. Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (pOBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS associado com carcinoma invasivo (CI adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE, receptor de progesterona (RP, receptor do fator de crescimento epidérmico humano 2 (HER2, citoqueratina 5/6 (CK5/6 e o receptor do fator de crescimento epidérmico (EGFR em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo, triplo-positivo (RE/RP/HER2-positivo, HER2-puro

  11. [Association of pulmonary carcinoma and ductal breast cancer].

    Science.gov (United States)

    El Khattabi, W; Lakhdar, N; Jabri, H; Afif, H

    2016-08-01

    Multiple primary cancers are relatively rare. The association between lung and breast cancer is exceptional and requires genetic research and predisposing factors. We report the case of a female patient of 43years, hospitalized for atelectasis of the left lung with breast lumps. Bronchial biopsies have concluded a primary lung adenocarcinoma. Breast biopsy objectified ductal invasive breast cancer. The treatment was a palliative chemotherapy. The evolution is marked by the early death of the patient. Although the association of multiple cancers is rare, their discovery requires a particular treatment regimen depends on the staging of each cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. 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.

  13. Improving Therapeutic Ratios with the Oncotype DX? Ductal Carcinoma In Situ (DCIS) Score

    OpenAIRE

    Lalani, Nafisha; Rakovitch, Eileen

    2017-01-01

    Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer comprising nearly 25% of breast cancer diagnoses in the mammographic era. Current guidelines recommend breast-conserving surgery followed by adjuvant radiotherapy; however, controversy exists regarding the appropriateness of these recommendations. Some women with DCIS will never recur, which raises the concern of over-treatment. Conversely, a small number of women will develop invasive recurrences, raising concerns of under-treat...

  14. Sentinel lymph node biopsy in patients with pure and high-risk ductal carcinoma in situ of the breast.

    Science.gov (United States)

    D'Eredità, Giovanni; Giardina, Carmela; Napoli, Anna; Ingravallo, Giuseppe; Troilo, Vito Leopoldo; Fischetti, Fernando; Berardi, Tommaso

    2009-01-01

    The role of sentinel lymph node biopsy in patients initially diagnosed with ductal carcinoma in situ resides in determining the predictors of invasive disease. The aim of the present study was to examine the incidence of sentinel lymph node metastases in a selected group of patients, with characteristics of high-risk ductal carcinoma in situ, in order to determine the clinical usefulness of sentinel lymph node biopsy. A total of 90 patients with a biopsy diagnosis of ductal carcinoma in situ were treated. Fifty-two patients with high-risk ductal carcinoma in situ had sentinel lymph node biopsy. The following characteristics of the primary tumor were considered as indicative of a risk of invasive disease: presence of palpable mass, mammographic mass, multicentric disease that required mastectomy, and histologically high nuclear grade or non-high nuclear grade with necrosis. Subdermal injections of 99mTc-labeled human albumin and subareolar injection of blue dye were used for sentinel lymph node identification. All sentinel nodes were sectioned serially and stained with hematoxylin and eosin. Immunohistochemical analysis was performed using a cytokeratin monoclonal antibody. A positive sentinel lymph node was found in only one patient (1.9%). The patient had a double lesion, and core-needle biopsy showed an atypical ductal hyperplasia and a intermediate degree of ductal carcinoma in situ. At pathologic review of the specimen, no invasive aspect was detected. The results of our study indicate that sentinel lymph node metastasis in pure ductal carcinoma in situ is extremely uncommon. We therefore suggest that sentinel lymph node biopsy might be indicated for patients with ductal carcinoma in situ detected as a palpable mass or as large extensive microcalcifications, as well as for patients who are undergoing mastectomy, especially with immediate reconstruction.

  15. In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer.

    Science.gov (United States)

    Alkatout, Ibrahim; Hübner, Friederike; Wenners, Antonia; Hedderich, Jürgen; Wiedermann, Meike; Sánchez, Cristina; Röcken, Christoph; Mathiak, Micaela; Maass, Nicolai; Klapper, Wolfram

    2017-04-01

    Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker. We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment. The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis. Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Role of the Radiotherapy Boost on Local Control in Ductal Carcinoma In Situ

    Directory of Open Access Journals (Sweden)

    Olivier Riou

    2012-01-01

    Full Text Available Ductal carcinoma in situ of the breast is associated with low mortality rates, but local relapse is a matter of concern in this disease. Risk factors for local relapse include young age, close or positive margins, and tumor necrosis. Whole breast irradiation following breast-conserving surgery for ductal carcinoma in situ significantly reduces the risk of local relapse as compared to breast-conserving surgery alone. Studies point to similar outcomes between breast-conserving surgery plus radiotherapy and mastectomy, in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for patients with invasive breast cancer. However, the effect of this strategy has never been prospectively reported for ductal carcinoma in situ. Two randomized controlled trials assessing this issue are ongoing. This paper represents an update on available literature about radiotherapy for DCIS with a special focus on the role of a radiotherapy boost to the tumor bed.

  17. Breaking down barriers: the importance of the stromal microenvironment in acquiring invasiveness in young women's breast cancer

    OpenAIRE

    Schedin, Pepper; Borges, Virginia

    2009-01-01

    Gene expression profiling was performed on laser captured breast stroma and epithelium obtained from 14 breast cancer patients. As with breast epithelium, of the stromal gene expression changes observed between normal tissue and invasive ductal carcinoma, greater than 90% occurred early, at the normal to ductal carcinoma in situ transition. Only 10% of stromal and 0% of epithelial genes were differentially regulated between non-invasive ductal carcinoma in situ and invasive disease. These dat...

  18. Nottingham grades of lobular carcinoma lack the prognostic implications they bear for ductal carcinoma.

    Science.gov (United States)

    Wachtel, Mitchell S; Halldorsson, Ari; Dissanaike, Sharmila

    2011-03-01

    Invasive lobular cancer (L) differs clinically and morphologically from invasive ductal cancer (D); differences notwithstanding, Nottingham grades are provided in both. This study compared 22,719 lobular carcinomas with 201,517 ductal carcinomas, dividing them into the grades: well differentiated (W), moderately differentiated (M), poorly differentiated (P), and ungraded to see if differences between comparable grades of lobular and ductal cancer were uniform, consistent with the notion the grading system provides similar information for both cancer subtypes. The Surveillance, Epidemiology and End Results (SEER) database was used to limn relationships among grades, as respects proportions of patients with T3 tumors and nodal metastases, as well as cancer-specific survival. Taken into account were age, estrogen and progesterone receptor status, and the administration of radiotherapy. More lobular than ductal carcinomas were T3; grades were not homogenous, with the incidence rate ratio (IRR) comparing lobular and ductal carcinomas being 8.2 for well differentiated, 4.1 for moderately differentiated, and 2.48 for poorly differentiated. With respect to nodal metastases, the 1.16 W L:W D IRR (P 0.05) and the 0.96 P L:P D IRR (P > 0.05) could have been due to chance. As respects survival, neither the 1.4 P L:P D time ratio (TR) (P 0.05) might have been due to chance. Grades of lobular carcinoma imply different meanings than do grades of ductal carcinoma. Studies of breast cancer should not assume commonality with respect to grade. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  20. [Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ].

    Science.gov (United States)

    Ruvalcaba-Limón, Eva; de Jesús Garduño-Raya, María; Bautista-Piña, Verónica; Trejo-Martínez, Claudia; Maffuz-Aziz, Antonio; Rodríguez-Cuevas, Sergio

    2014-01-01

    Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

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

    Science.gov (United States)

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

    2016-02-17

    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, or whether there are differences in the strength of association for shared loci. 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. Most (67 %) 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 receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

  2. 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.

  3. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina

    2012-01-01

    Introduction: Vascular endothelial growth factor A (VEGF-A) is a very important growth factor in angiogenesis and holds the potential as both a predictive marker for anti-angiogenic cancer treatment and as a prognostic variable. Consequently, reliable estimation of VEGF expression is crucial....... Material and methods: We immunostained whole tumor sections for VEGF-A, -B, and VEGFR-1 of invasive ductal carcinomas of the breast and scored the tumors manually by staining intensity as the only parameter and by a combination of qualitative and quantitative staining information. We also introduced...... measurements of VEGF-A, VEGF-B and VEGFR-1 when analyzing whole tumor sections of invasive ductal breast carcinomas....

  4. Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors

    NARCIS (Netherlands)

    Truin, Wilfred; Roumen, Rudi M.H.; Siesling, Sabine; van de Vijver, Koen K.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    Background Differences in estrogen (ER) and progesterone (PR) expression between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) could be an underlying reason for the difference in chemo-sensitivity and response to hormonal therapy between ILC and IDC. The aim of this study was

  5. Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?

    Science.gov (United States)

    Krantz, Benjamin A; O'Reilly, Eileen M

    2017-12-21

    Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the number of trials in mid to late-stage with integrated biomarkers. Additionally, blood based biomarkers that provide a measure of disease activity and allow for minimally invasive tumor analyses are emerging, including circulating tumor DNA, exosomes and circulating tumor cells. In this article, we will review potential biomarkers for currently approved therapies as well as emerging biomarkers for therapeutics under development. Copyright ©2017, American Association for Cancer Research.

  6. 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

  7. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

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

    2014-01-01

    . 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...... of transcriptional and translation regulatory mechanisms and the disparities between genomic and proteomic data from the same samples. In this study, we have examined tumor antigens as potential biomarkers for breast cancer using genomics and proteomics data from previously reported laser capture microdissected ER...

  8. Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases

    Science.gov (United States)

    Khoury, Thaer; Hu, Qiang; Liu, Song; Wang, Jianmin

    2015-01-01

    Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study is to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ, or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with 4 of 5 concurrent ductal carcinoma in situ cases and with 2 of 2 invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ then by invasive ductal carcinoma (p=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs. without invasive ductal carcinoma, the former had 11q22.1 to 11q23.3 loss (p=0.031) and chr5 gain (p=0.085) and enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs. without ductal carcinoma in situ, the former had gain in 5q35.3 (p=0.041), 8q24.3 (p=0.041), and 21q13.2 to 21q13.31 (p=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, while intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this

  9. Expression of metallothionein 3 in ductal breast cancer.

    Science.gov (United States)

    Gomulkiewicz, Agnieszka; Jablonska, Karolina; Pula, Bartosz; Grzegrzolka, Jedrzej; Borska, Sylwia; Podhorska-Okolow, Marzenna; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Ugorski, Maciej; Zabel, Maciej; Dziegiel, Piotr

    2016-12-01

    Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.

  10. 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.

  11. The 3-layered ductal epithelium in gynecomastia.

    Science.gov (United States)

    Kornegoor, Robert; Verschuur-Maes, Anoek H J; Buerger, Horst; van Diest, Paul J

    2012-05-01

    Gynecomastia is the most common abnormality in the male breast and has been associated with male breast cancer, but whether there is an etiological role remains unknown. In the present study we conducted an immunohistochemical investigation to further characterize gynecomastia. A total of 46 cases of gynecomastia were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor, HER2, androgen receptor, cytokeratins (CK5, CK14, CK7, and CK8/18), p63, E-cadherin, BRST2, cyclin D1, Bcl-2, p53, p16, p21, and Ki67. In addition, 8 cases of male ductal carcinoma in situ and normal breast tissue obtained from autopsies (n=10) and adjacent to male breast cancer (n=5) were studied. Normal ductal male breast epithelial cells were very often ER and Bcl-2 positive (>69%), and progesterone receptor and androgen receptor expression was also common (>39%). Gynecomastia showed a consistent 3-layered pattern: 1 myoepithelial and 2 epithelial cell layers with a distinctive immunohistochemical staining pattern. The intermediate luminal layer, consisting of vertically oriented cuboidal-to-columnar cells, is hormone receptor positive and expresses Bcl-2 and cyclin D1. The inner luminal layer is composed of smaller cells expressing CK5 and often CK14 but is usually negative for hormone receptors and Bcl-2. Male ductal carcinoma in situ was consistently ER positive and CK5/CK14 negative. In conclusion, for the first time we describe the 3-layered ductal epithelium in gynecomastia, which has a distinctive immunohistochemical profile. These results indicate that different cellular compartments exist in gynecomastia, and therefore gynecomastia does not seem to be an obligate precursor lesion of male breast cancer.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina

    2011-01-01

    Vascular endothelial growth factor A (VEGF-A) is a very important growth factor in angiogenesis and holds the potential as both a predictive marker for anti-angiogenic cancer treatment and as a prognostic variable. Consequently, reliable estimation of VEGF expression is crucial. We immunostained...... whole tumor sections for VEGF-A, -B, and VEGFR-1 of invasive ductal carcinomas of the breast and scored the tumors manually with staining intensity as the only parameter and by a combination of qualitative and quantitative information. We also introduce an automated method for analyzing VEGF expression...

  17. Breast ductal carcinoma metastasis to jaw bones: a case report

    Directory of Open Access Journals (Sweden)

    Mahmood Reza AshabYamin

    2014-04-01

    Full Text Available Malignant tumors of the oral cavity which are metastatic are very rare and consist of 1% of malignancies of the oral cavity. Numbness or paresthesia of the lower lip or the chin is the main feature of presence of metastasis in the jaw. Our patient was a 38 year old woman with chief complaint of pain in the right half of her face, jaw and teeth. Her medical history revealed a radical mastectomy with lymphadenectomy in the left breast because of invasive ductal carcinoma grade II/III and stage IIIA (T2N2M0 without distant metastasis, followed by chemotherapy (before and after the surgery and radiotherapy two years ago. Following complementary examinations a malignant bone lesion in particular osteosarcoma was suspected. According to this evidence, possibility of early diagnosis of malignant tumors is very important for dentists and maxillofacial surgeons. Symptoms such as paresthesia of the lip and chin is very helpful in differential diagnosis of metastatic lesions from other similar clinical cases especially in patients with history of malignancies which minimize surgical and mental injuries and increase life expectancy of patients.

  18. Pituitary Tumor-Transforming Gene 1 Is Expressed in Primary Ductal Breast Carcinoma, Lymph Node Infiltration, and Distant Metastases

    Directory of Open Access Journals (Sweden)

    Fabio Grizzi

    2013-01-01

    Full Text Available Despite the advances that have been made in the fields of molecular and cell biology, there is still considerable debate explaining how the breast cancer cells progress through carcinogenesis and acquire their metastatic ability. The lack of preventive methods and effective therapies underlines the pressing need to identify new biomarkers that can aid early diagnosis and may be targets for effective therapeutic strategies. In this study we explore the pituitary tumor-transforming gene 1 (PTTG1 expression in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Three human cell lines, 184B5 derived from normal mammary epithelium, HCC70 from a primary ductal carcinoma, and MDA-MB-361 from a breast metastasis, were used for quantifying PTTG1 mRNA expression. The PTTG1 immunohistochemical expression was carried out on specimens taken from eight patients with invasive ductal breast cancer who underwent surgical treatment and followup for five years retrospectively selected. The study demonstrated that PTTG1 is expressed gradually in primary ductal breast carcinoma, lymph node infiltration, and distant metastases. Our findings suggest that the immunohistochemical evaluation of PTTG1 expression might be a powerful biomarker of recognition and quantification of the breast cancer cells in routine pathological specimens and a potential target for developing an effective immunotherapeutic strategy for primary and metastatic breast cancer.

  19. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies

    Directory of Open Access Journals (Sweden)

    Aleksandra Adamska

    2017-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC, which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms and prolonging survival. Currently, available therapeutic options are surgery, radiation, chemotherapy, immunotherapy, and use of targeted drugs. However, thus far, therapies targeting cancer-associated molecular pathways have not given satisfactory results; this is due in part to the rapid upregulation of compensatory alternative pathways as well as dense desmoplastic reaction. In this review, we summarize currently available therapies and clinical trials, directed towards a plethora of pathways and components dysregulated during PDAC carcinogenesis. Emerging trends towards targeted therapies as the most promising approach will also be discussed.

  20. THE SUBTYPES OF PANCREATIC DUCTAL ADENOCARCINOMAS

    Directory of Open Access Journals (Sweden)

    Apeksha Kakkar

    2016-12-01

    Full Text Available Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients.

  1. A rare case of extensive ductal carcinoma in situ of the breast with secretory features

    Directory of Open Access Journals (Sweden)

    Kenichi Sugihara

    2012-10-01

    Full Text Available We report a very rare case of extensive ductal carcinoma in situ (DCIS of the breast with secretory features in a 30-year old Japanese woman. The patient presented with a nodule in the lower inner quadrant of the left breast measuring approximately 2-3 cm, accompanied by an irregular tumor shadow with segmental microcalcification on mammography. These findings suggested malignancy, and excisional biopsy was performed following core needle biopsy. Pathological diagnosis was that of DCIS with secretory features. A treatment plan of simple mastectomy and sentinel lymph node biopsy was chosen. Most previous reports have only described invasive secretory carcinoma of the breast. We have only been able to find 2 case reports of non-invasive secretory lesion in the English literature to date. Because the characteristics of this lesion are not widely known, we thought it important to share our findings.

  2. Improving Therapeutic Ratios with the Oncotype DX® Ductal Carcinoma In Situ (DCIS) Score.

    Science.gov (United States)

    Lalani, Nafisha; Rakovitch, Eileen

    2017-04-21

    Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer comprising nearly 25% of breast cancer diagnoses in the mammographic era. Current guidelines recommend breast-conserving surgery followed by adjuvant radiotherapy; however, controversy exists regarding the appropriateness of these recommendations. Some women with DCIS will never recur, which raises the concern of over-treatment. Conversely, a small number of women will develop invasive recurrences, raising concerns of under-treatment. Currently, several clinical and pathologic factors have been identified as prognostic markers for recurrence; however, these variables alone have been unable to identify low-risk and high-risk subgroups. The Oncotype DX® DCIS score is a multigene assay which allows for the addition of molecular information to traditional clinical and pathologic factors to help guide treatment decisions. Here, we present two case examples illustrating the use of the Oncotype DCIS score in clinical practice.

  3. The clinicopathological significance of forkhead box P1 and forkhead box O3a in pancreatic ductal adenocarcinomas.

    Science.gov (United States)

    Luo, Xin; Yang, Zhulin; Liu, Xiao; Liu, Ziru; Miao, Xiongying; Li, Daiqiang; Zou, Qiong; Yuan, Yuan

    2017-05-01

    Pancreatic ductal adenocarcinoma is a highly malignant tumor with poor prognosis, and the biomarkers for the early diagnosis, targeting therapy, and prognosis are still not clinically available. This study investigated the expression of forkhead box P1 and forkhead box O3a proteins in human pancreatic ductal adenocarcinoma tumor tissues and pancreatic tissues with and without benign lesions using immunohistochemical staining. Results showed that the positive rates of forkhead box P1 and forkhead box O3a protein expression were significantly lower in pancreatic ductal adenocarcinoma tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (p box P1 and forkhead box O3a protein expression exhibited dysplasia or intraepithelial neoplasia. The positive rates of forkhead box P1 and forkhead box O3a expression were significantly lower in cases with tumor mass >5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and tumor-node-metastasis III + IV stage disease compared to cases with tumor mass ⩽5 cm (p box P1 and forkhead box O3a expression survived significantly shorter than patients with positive forkhead box P1 and forkhead box O3a expression (p = 0.000). Cox multivariate analysis revealed that negative forkhead box P1 and forkhead box O3a expression was an independent poor prognosis factor in pancreatic ductal adenocarcinoma patients. The area under the curve of a receiver operating characteristic curve was 0.642 for forkhead box P1 (95% confidence interval: 0.553-0.730) and 0.655 for forkhead box O3a (95% confidence interval: 0.6568-0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas.

  4. 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.

  5. BRCA mutations in women with ductal carcinoma in situ.

    Science.gov (United States)

    Smith, Karen Lisa; Adank, Muriel; Kauff, Noah; Lafaro, Kelly; Boyd, Jeff; Lee, Johanna B; Hudis, Clifford; Offit, Kenneth; Robson, Mark

    2007-07-15

    The strength of the association between ductal carcinoma in situ (DCIS) and BRCA mutations has not been defined. Mutation frequency was compared in three groups: (1) a prevalent series of women with DCIS, (2) an incident series of women with DCIS, and (3) a clinic-based series of women with DCIS referred for hereditary cancer risk assessment. In groups 1 and 2, limited to Ashkenazi Jewish (AJ) cases, mutation frequency was compared with that in age-matched AJ controls with invasive breast cancer (IBC). In group 1, 3 of 62 (4.8%) women with DCIS and 15 of 130 (11.5%) controls with IBC had BRCA mutations. In group 2, 0 of 58 (0%) women with DCIS and 6 of 116 (5.2%) controls with IBC had BRCA mutations [combined odds ratios (OR) in groups 1 and 2: 3.64, 95% confidence interval (95% CI), 1.06-12.46; P=0.04]. In group 3, deleterious mutations were identified in 10 of 79 (12.7%) probands with DCIS, similar to the frequency in IBC probands. In group 3, mutations were associated with family history of ovarian cancer (OR, 13.35; 95% CI, 2.48-71.94; P=0.003) or early onset breast cancer (OR, 16.23; 95% CI, 1.68-157.01; P=0.02) but not with AJ ethnicity or age at diagnosis. BRCA mutations were less frequent in women with DCIS not selected for family history or age at diagnosis than in women with IBC. Nonetheless, mutations were found in a significant proportion of women with DCIS who presented for hereditary risk assessment.

  6. 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.

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

    OpenAIRE

    Sobinsky, Justin D.; Thomas D. Willson; 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...

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

    Science.gov (United States)

    Doyle, B; Al-Mudhaffer, M; Kennedy, M M; O'Doherty, A; Flanagan, F; McDermott, E W; Kerin, M J; Hill, A D; Quinn, C M

    2009-06-01

    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. To examine the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. 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. 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 NCB were predictive of invasive carcinoma in the excision specimen. 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.

  9. Ductal carcinoma in situ of the breast

    Directory of Open Access Journals (Sweden)

    Jennifer L. Peterson

    2011-12-01

    Full Text Available Ductal carcinoma in situ (DCIS of the breast is a noninvasive form of breast cancer that has increased in incidence over the past several decades secondary to screening mammography. DCIS now represents 20–30% of all newly diagnosed cases of breast cancer. Patients with DCIS typically present with an abnormal mammogram, and diagnosis is most commonly obtained with an imageguided biopsy. Historically, mastectomy was considered the primary curative option for patients with DCIS. However, treatment of DCIS continues to evolve, and now treatment strategies also include breast-conserving therapy, which consists of local excision followed by radiation therapy or local excision alone. Multiple randomized trials have confirmed a decrease in ipsilateral breast tumor recurrence in patients treated with local excision followed by radiation therapy compared with local excision alone. Ongoing clinical trials attempt to identify a subgroup of DCIS patients at low risk for recurrence who may not benefit from radiation therapy. In addition, because the majority of ipsilateral breast tumor recurrences occur near the original primary tumor site, partial breast irradiation is currently under investigation as a treatment option for DCIS patients. Randomized trials have shown tamoxifen can reduce the risk of ipsilateral and contralateral breast tumor recurrences while the role of aromatase inhibitors is the subject of current clinical trials. DCIS represents a complex pathologic entity, and treatment optimization requires a multidisciplinary approach.

  10. Genetics and biology of pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Ying, Haoqiang; Dey, Prasenjit; Yao, Wantong; Kimmelman, Alec C.; Draetta, Giulio F.; Maitra, Anirban; DePinho, Ronald A.

    2016-01-01

    With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival. PMID:26883357

  11. 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.

  12. SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.

    Science.gov (United States)

    Peuhu, Emilia; Kaukonen, Riina; Lerche, Martina; Saari, Markku; Guzmán, Camilo; Rantakari, Pia; De Franceschi, Nicola; Wärri, Anni; Georgiadou, Maria; Jacquemet, Guillaume; Mattila, Elina; Virtakoivu, Reetta; Liu, Yuming; Attieh, Youmna; Silva, Kathleen A; Betz, Timo; Sundberg, John P; Salmi, Marko; Deugnier, Marie-Ange; Eliceiri, Kevin W; Ivaska, Johanna

    2017-01-17

    SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin cpdm ), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin cpdm mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin cpdm mice displayed reduced collagen arrangement and extracellular matrix (ECM) stiffness. Moreover, Sharpin cpdm mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM. © 2016 The Authors.

  13. Synchronous papillary thyroid carcinoma and breast ductal carcinoma: A rare case report and literature review.

    Science.gov (United States)

    Zhong, Jinjing; Lei, Jianyong; Jiang, Ke; Li, Zhihui; Gong, Rixiang; Zhu, Jingqiang

    2017-02-01

    The incidences of both thyroid cancer and breast cancer have been rising in recent years; however, it is very rare to find a single person with both of these cancers. Only a few cases of synchronous thyroid and breast cancer have been published, and even fewer cases have been reported in older patients (>60 years). The current study presents a case of synchronous papillary thyroid carcinoma and breast ductal carcinoma in an elderly patient. The patient first underwent a mastectomy and axillary lymphadenectomy in our department, followed by a total thyroidectomy and lymphadenectomy of the left lateral region of the neck 1 month later. Postoperative pathological examination identified invasive ductal carcinoma of the breast and papillary carcinoma of the thyroid. Over almost half a year of follow-up, the patient has exhibited no evidence of recurrence or metastasis, as demonstrated by careful ultrasound examinations. Herein, we not only report this case but also present a systematic review of the causes, diagnosis, and treatment of synchronous breast and thyroid cancer. Although synchronous primary tumors of the thyroid and breast are very rare, they remain a possibility; therefore, more attention should be paid to these cases.

  14. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853. EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group

    NARCIS (Netherlands)

    Julien, J. P.; Bijker, N.; Fentiman, I. S.; Peterse, J. L.; Delledonne, V.; Rouanet, P.; Avril, A.; Sylvester, R.; Mignolet, F.; Bartelink, H.; van Dongen, J. A.

    2000-01-01

    BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography. Since selected women with invasive cancer can be treated safely with breast conservation therapy it is

  15. 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

    of postoperative pain, sensory disturbances, psychological distress and rehabilitation needs among Danish women with DCIS. METHODS: A total of 574 women treated for DCIS in Denmark in 2013 and 2014 were enrolled and 473 (82%) completed a detailed questionnaire on demographic factors, pain, sensory disturbances......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......, psychological aspects and rehabilitation needs 1-3 years after surgery. RESULTS: Median age was 60 years. A total of 33% of patients reported any pain and 12% reported moderate to severe pain in the area of surgery. Younger age (

  16. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina

    2012-01-01

    . Material and methods: We immunostained whole tumor sections for VEGF-A, -B, and VEGFR-1 of invasive ductal carcinomas of the breast and scored the tumors manually by staining intensity as the only parameter and by a combination of qualitative and quantitative staining information. We also introduced...... an automated method for analyzing VEGF expression (so-called AI score) using the same tumor sections. Analysis of 100% of the tumor area was performed and the results were compared to the reduced analysis of 25% of the tumor area. These analyses were performed at 5x and 10x magnification and each analysis...... was repeated in a second run with a new delineation of the tumor area. Results: We found that the AI scores were correlated to the manual scoring of VEGF intensity, but the reproducibility of manual IHC scores was rather poor. The AI scores were reproducible and the restricted analysis of 25% of the tumor area...

  17. Estimation of Immunohistochemical Expression of VEGF in Ductal Carcinomas of the Breast

    DEFF Research Database (Denmark)

    Maae, Else; Nielsen, Martin; Dahl Steffensen, Karina

    2011-01-01

    whole tumor sections for VEGF-A, -B, and VEGFR-1 of invasive ductal carcinomas of the breast and scored the tumors manually with staining intensity as the only parameter and by a combination of qualitative and quantitative information. We also introduce an automated method for analyzing VEGF expression...... (so-called AI score) using the same tumor sections. Analysis of 100% of the tumor area was performed and the results were compared to the reduced analysis of 25% of the tumor area. These analyses were performed at 5x and 10x magnification and each analysis was repeated in a second run with a new...... delineation of the tumor area. We found that the AI scores were correlated to the manual scoring of VEGF intensity, but reproducibility of manual IHC scores was rather poor. The AI scores were reproducible and the restricted analysis of 25% of the tumor area at 5x magnifications was the most efficient...

  18. Radiation Therapy Following Breast Conserving Surgery for Ductal Carcinoma in situ: Yes or No?

    Science.gov (United States)

    Stoleru, Liviu Sorin; Stoleru, Smaranda

    2017-01-01

    Ductal carcinoma in situ (DCIS) is a non-invasive precursor to breast cancerand represents a heterogenous group of lesions with different malignant potential. Despite several randomized trials, there is still controversy regarding the optimal local treatment for DCIS patients. The addition of radiotherapy after breast conserving surgery approximately halves the local recurrence risk but has no impact on long-term survival. Clinical studies failed to identify a low risk subgroup of DCIS patients treated with breast conserving surgery in whom radiotherapy can be safely omitted. Results of clinical trials of breast conserving surgery radiotherapy are summarized. Treatment decision making in low risk DCIS and current tendencies in the radiotherapy for DCIS are other issues addressed in this paper. Celsius.

  19. Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?

    Science.gov (United States)

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

    2017-03-01

    Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic features to predict upstaging of DCIS. The goal was to provide intentionally conservative baseline performance using readily available data from radiologists and pathologists and only linear models. We conducted a retrospective analysis on 99 patients with DCIS. Of those 25 were upstaged to invasive cancer at the time of definitive surgery. Pre-operative factors including both the histologic features extracted from stereotactic core needle biopsy (SCNB) reports and the mammographic features annotated by an expert breast radiologist were investigated with statistical analysis. Furthermore, we built classification models based on those features in an attempt to predict the presence of an occult invasive component in DCIS, with generalization performance assessed by receiver operating characteristic (ROC) curve analysis. Histologic features including nuclear grade and DCIS subtype did not show statistically significant differences between cases with pure DCIS and with DCIS plus invasive disease. However, three mammographic features, i.e., the major axis length of DCIS lesion, the BI-RADS level of suspicion, and radiologist's assessment did achieve the statistical significance. Using those three statistically significant features as input, a linear discriminant model was able to distinguish patients with DCIS plus invasive disease from those with pure DCIS, with AUC-ROC equal to 0.62. Overall, mammograms used for breast screening contain useful information that can be perceived by radiologists and help predict occult invasive components in DCIS.

  20. Outcomes of robotic surgery for pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Zhan, Qian; Deng, Xiaxing; Weng, Yuanchi; Jin, Jiabin; Wu, Zhichong; Li, Hongwei; Shen, Baiyong

    2015-01-01

    Background To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and

  1. Predictive factors for breast cancer in patients diagnosed atypical ductal hyperplasia at core needle biopsy

    Directory of Open Access Journals (Sweden)

    Lee Ahwon

    2009-10-01

    Full Text Available Abstract Background Percutaneous core needle biopsy (CNB is considered to be the standard technique for histological diagnosis of breast lesions. But, it is less reliable for diagnosing atypical ductal hyperplasia (ADH. The purpose of the present study was to predict, based on clinical and radiological findings, which cases of ADH diagnosed by CNB would be more likely to be associated with a more advanced lesion on subsequent surgical excision. Methods Between February 2002 and December 2007, consecutive ultrasound-guided CNBs were performed on suspicious breast lesions at Seoul St. Mary's Hospital. A total of 69 CNBs led to a diagnosis of ADH, and 45 patients underwent follow-up surgical excision. We reviewed the medical records and analyses retrospectively. Results Sixty-nine patients were diagnosed with ADH at CNB. Of these patients, 45 underwent surgical excision and 10 (22.2% were subsequently diagnosed with a malignancy (ductal carcinoma in situ, n = 8; invasive cancer, n = 2. Univariate analysis revealed age (≥ 50-years at the time of core needle biopsy (p = 0.006, size (> 10 mm on imaging (p = 0.033, and combined mass with microcalcification on sonography (p = 0.029 to be associated with underestimation. When those three factors were included in multivariate analysis, only age (p = 0.035, HR 6.201, 95% CI 1.135-33.891 was an independent predictor of malignancy. Conclusion Age (≥ 50 at the time of biopsy is an independent predictive factor for breast cancer at surgical excision in patients with diagnosed ADH at CNB. For patients diagnosed with ADH at CNB, only complete surgical excision is the suitable treatment option, because we could not find any combination of factors that can safely predict the absence of DCIS or invasive cancer in a case of ADH.

  2. Genetic control of ductal morphology, estrogen-induced ductal growth, and gene expression in female mouse mammary gland.

    Science.gov (United States)

    Wall, Emma H; Case, Laure K; Hewitt, Sylvia C; Nguyen-Vu, Trang; Candelaria, Nicholes R; Teuscher, Cory; Lin, Chin-Yo

    2014-08-01

    The uterotropic response of the uterus to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous genetic studies from our laboratory using inbred mice that are high (C57BL6/J; B6) or low (C3H/HeJ; C3H) responders to E2 led to the identification of quantitative trait loci (QTL) associated with phenotypic variation in uterine growth and leukocyte infiltration. Like the uterus, phenotypic variation in the responsiveness of the mammary gland to E2 during both normal and pathologic conditions has been reported. In the current experiment, we utilized an E2-specific model of mammary ductal growth combined with a microarray approach to determine the degree to which genotype influences the responsiveness of the mammary gland to E2, including the associated transcriptional programs, in B6 and C3H mice. Our results reveal that E2-induced mammary ductal growth and ductal morphology are genetically controlled. In addition, we observed a paradoxical effect of mammary ductal growth in response to E2 compared with what has been reported for the uterus; B6 is a high responder for the uterus and was a low responder for mammary ductal growth, whereas the reverse was observed for C3H. In contrast, B6 was a high responder for mammary ductal side branching. The B6 phenotype was associated with increased mammary epithelial cell proliferation and apoptosis, and a distinct E2-induced transcriptional program. These findings lay the groundwork for future experiments designed to investigate the genes and mechanisms underlying phenotypic variation in tissue-specific sensitivity to systemic and environmental estrogens during various physiological and disease states.

  3. Mammary Ductal Carcinoma In Situ: A Fresh Look at Architectural Patterns

    Directory of Open Access Journals (Sweden)

    Gabriel Scripcaru

    2012-01-01

    Full Text Available Mammary ductal carcinoma in-situ (DCIS, a malignant appearing lesion on cytological and histological grounds, is in fact a non-obligate precancer. DCIS is difficult to manage and is sometimes treated more aggressively than invasive carcinoma. Although most DCIS classifications take into account the architectural growth pattern, when it comes to architecture, the literature is full of contradictory information. We examined 289 breast cancers and found DCIS in 265 of the cases. The majority of the DCIS cases were seen in the setting of invasive cancer and only 9% of the cases represented pure DCIS with no invasive cancer. The DCIS commonly displayed a mixed pattern with micropapillary, cribriform and solid components with the micropapillary type being the rarest, occurring seldom on its own. A continuum of growth with a micropapillary pattern evolving into a cribriform type could be seen in some of the cases. This may explain some of the conflicting information, in the literature, regarding the different architectural types of DCIS. The comedo-pattern of necrosis could be seen in all types of DCIS. We therefore conclude that the study of the determinants of growth pattern in DCIS would be the key to unravelling the diverse, often non-concordant evidence one encounters in the literature.

  4. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    Science.gov (United States)

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  5. Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic ballooning of acinar and ductal epithelium?

    Science.gov (United States)

    Singhi, Aatur D; Norwood, Stephanie; Liu, Ta-Chiang; Sharma, Rajni; Wolfgang, Christopher L; Schulick, Richard D; Zeh, Herbert J; Hruban, Ralph H

    2013-09-01

    Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non-neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic transformation." In subsequent studies, these lesions were given the designation of "-oma," despite the relative lack of evidence supporting a neoplastic process. To characterize these lesions further, we examined the clinical, pathologic, and immunohistochemical features of 8 ACAs. The majority of patients were female (7 of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15 cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of acinar and ductal epithelium. Immunolabeling, including double-labeling for cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and acinar cells lining the cysts. In some areas, the cysts with patches of acinar and ductal differentiation formed larger locules with incomplete septa as they appeared to fuse with other cysts. In contrast, the unilocular cases were lined by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium. Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated invasive carcinoma were absent in all cases. In addition, we assessed the clonal versus polyclonal nature of ACAs, occurring in women, using X-chromosome inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases were informative and demonstrated a random X-chromosome inactivation pattern. Clinical follow-up information was available for all patients, and follow-up ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence or malignant transformation. We hypothesize that early lesions are marked by acinar dilatation that expands into and incorporates smaller ductules and later larger ducts

  6. 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.

  7. 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

  8. 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.

  9. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer

    NARCIS (Netherlands)

    Michaut, M; Chin, SF; Majewski, I; Severson, TM; Bismeijer, T; de Koning, L; Peeters, JK; Schouten, PC; Rueda, OM; Bosma, AJ; Wessels, L.F.A.; Authors, More

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a

  10. On the development of the hepatopancreatic ductal system.

    Science.gov (United States)

    Villasenor, Alethia; Stainier, Didier Y R

    2017-06-01

    The hepatopancreatic ductal system is the collection of ducts that connect the liver and pancreas to the digestive tract. The formation of this system is necessary for the transport of exocrine secretions, for the correct assembly of the pancreatobiliary ductal system, and for the overall function of the digestive system. Studies on endoderm organ formation have significantly advanced our understanding of the molecular mechanisms that govern organ induction, organ specification and morphogenesis of the major foregut-derived organs. However, little is known about the mechanisms that control the development of the hepatopancreatic ductal system. Here, we provide a description of the different components of the system, summarize its development from the endoderm to a complex system of tubes, list the pathologies produced by anomalies in its development, as well as the molecules and signaling pathways that are known to be involved in its formation. Finally, we discuss its proposed potential as a multipotent cell reservoir and the unresolved questions in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Squamous cell carcinoma of the nipple following radiation therapy for ductal carcinoma in situ: a case report

    Directory of Open Access Journals (Sweden)

    Huang Yajue

    2010-06-01

    Full Text Available Abstract Introduction Radiation-induced nonmelanoma skin cancer was first reported seven years after the discovery of X-rays, but has received relatively little consideration in the literature. Specifically, nonmelanoma skin cancer after conservative surgery and radiation for early stage breast cancer has not been well studied. We report the case of a woman who developed squamous cell carcinoma of the nipple nine years after conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. We also review the relevant literature available to date. Case presentation A 66-year-old African-American woman presented to the hospital with a non-healing ulcer of the right nipple. Her past medical history was significant for right breast ductal carcinoma in situ for which she had undergone lumpectomy and whole breast radiation therapy nine years previously. Mammography and magnetic resonance imaging studies were negative for recurrent breast cancer. However, the latter demonstrated abnormal enhancement in the nipple-areolar region. An incisional biopsy of the lesion demonstrated invasive squamous cell carcinoma. Subsequently, the patient underwent wide excision of the nipple-areolar complex. Sentinel lymph-node biopsy was offered but our patient declined. She was considered to have local disease and hence no further treatment was recommended. Conclusion This case represents the first reported occurrence of squamous cell carcinoma of the nipple to follow conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. It is likely that radiation overexposure resulted in a radiation burn and subsequent radiodermatitis, placing it at risk for squamous cell carcinoma. A diagnosis of squamous cell carcinoma should be considered in a patient with a nipple lesion following radiation therapy for breast cancer.

  12. 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 carcinoma in situ identified with 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C. [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Quan, Liao; Yupei, Zhao [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking (China); Friess, Helmut [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Erkan, Mert, E-mail: erkan@chir.med.tu-muenchen.de [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany); Kleeff, Joerg [Department of Surgery, Technische Universitaet Muenchen, Munich (Germany)

    2010-10-22

    Research highlights: {yields} The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. {yields} Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. {yields} BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. {yields} 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

  14. Oral inverted ductal papilloma: not related to HPV.

    Science.gov (United States)

    Do Canto, Alan Motta; Mistro, Florence Zumbaio; Kignel, Sergio; Martins, Fabiana; Palmieri, Michelle; Braz-Silva, Paulo Henrique

    2017-03-15

    Oral inverted ductal papilloma (OIDP) is a rare, nonrecurrent,benign lesion of salivary glands. The etiologyis still poorly understood; the correlation with humanpapilloma virus (HPV) is controversial. Herein wepresent a 74-year-old man with a tumor in lower lip.Incisional biopsy was performed and the histologicaldiagnosis was OIDP. Inno-LiPA assay, based onpolymerase chain reaction and in situ hybridizationwas used to assess for HPV with no detection of viralDNA. Surgical excision was performed without anyrecurrences after two years of follow-up.

  15. An uncommon presentation of ductal carcinoma in situ

    Science.gov (United States)

    Motindi, Rodney; Mallon, Peter; Dace, Stephen

    2012-01-01

    A 47-year-old woman presented with 6 weeks history of non-blood-stained nipple discharge. Two separate nipple cytology assessments revealed malignant cells despite normal clinical examination and radiological investigation (mammogram, ultrasound and MRI). The patient elected for a central segmentectomy which revealed a 1.8 cm area of high-grade comedo ductal carcinoma in situ in the subareolar region. The patient made a good postoperative recovery. 6 months follow-up revealed a 5 mm area of new calcification, core biopsy revealed atypical cells. After counselling, the patient elected for bilateral mastectomy which revealed fibrocystic tissue only. PMID:23001103

  16. In Situ Ductal Carcinoma Arising in Benign Phyllodes Tumor in 19-Year Old Patient: A Case Report

    Science.gov (United States)

    Çolakoğlu, Muhammet Kadri; Yenidoğan, Erdinç; Akgül, Gökhan Giray; Irkkan, Sultan Çiğdem; Özdemir, Yılmaz; Gülçelik, Mehmet Ali; Çamlıbel, Mithat

    2014-01-01

    Phyllodes tumors are fibroepithelial lesions and malign forms are rare neoplasms with lower than 1% of all primary breast tumors. Malign forms are usually behaves like sarcomas because they occur in the stroma of the breast. Also proliferation of epithelium occurs and even it is less often, the epithelial component of phyllodes tumors can transform into malignancy too. This epithelial malignancies are usually in the form of infiltrative carcinomas and non-invasive tumors arising in benign phyllodes tumors are much rarer but can be seen. Literature include very few cases about this situation and cases are usually old woman. We report a 19-year old patient who was diagnosed with ductal carcinoma in situ arising in benign phyllodes tumor of the breast. PMID:28331678

  17. Ductal carcinoma in situ: a brief review of treatment variation and impacts on patients and society.

    Science.gov (United States)

    Vatovec, Christine; Erten, Mujde Z; Kolodinsky, Jane; Brown, Phil; Wood, Marie; James, Ted; Sprague, Brian L

    2014-01-01

    Nearly 20% of all breast cancer cases are ductal carcinoma in situ (DCIS), with over 60,000 cases diagnosed each year. Many of these cases would never cause clinical symptoms or threaten the life of the woman; however, it is currently impossible to distinguish which lesions will progress to invasive disease from those that will not. DCIS is generally associated with an excellent prognosis regardless of the treatment pathway, but there is variation in treatment aggressiveness that seems to exceed the medical uncertainty associated with DCIS management. Therefore, it would seem that a significant proportion of women with DCIS receive more extensive treatment than is needed. This overtreatment of DCIS is a growing concern among the breast cancer community and has implications for both the patient (via adverse treatment-related effects, as well as out-of-pocket costs) and society (via economic costs and the public health and environmental harm resulting from health care delivery). This article discusses DCIS treatment pathways and their implications for patients and society and calls for further research to examine the factors that are leading to such wide variation in treatment decisions.

  18. Spatial distribution of mast cells and macrophages around tumor glands in human breast ductal carcinoma.

    Science.gov (United States)

    Tamma, Roberto; Guidolin, Diego; Annese, Tiziana; Tortorella, Cinzia; Ruggieri, Simona; Rega, Serena; Zito, Francesco A; Nico, Beatrice; Ribatti, Domenico

    2017-10-01

    Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Identifying three different architectural subtypes of mammary ductal carcinoma in situ using multiphoton microscopy

    Science.gov (United States)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, shuangmu; Wang, Chuan; Chen, Jianxin

    2015-10-01

    Ductal carcinoma in situ (DCIS) is often considered as the precursor of invasive breast cancer, and the risk of DCIS progression to IBC has been estimated based on the evaluation of pathological features, among which the architectural subtype is the most common one. In this study, multiphoton microscopy (MPM) is applied to identify three different architectural subtypes of DCIS (solid, cribriform and comedo). It is found that MPM has the capability to visualize the proliferating pattern of tumor cells, the presence of intraluminal necrosis and the morphology of basement membrane, which are all taken into account in subtyping DCIS. In addition, MPM also can be used to quantify the cellular metabolism, for quantitatively identifying tumor staging during tumor progression. This result highlights the potential of MPM as an advanced technique to assess the pathological characters of the breast tumor in real-time and reflect the degree of tumor progression in vivo, by integrating into the intra-fiberoptic ductoscopy or transdermal biopsy needle.

  20. Automated reconstruction algorithm for identification of 3D architectures of cribriform ductal carcinoma in situ.

    Directory of Open Access Journals (Sweden)

    Kerri-Ann Norton

    Full Text Available Ductal carcinoma in situ (DCIS is a pre-invasive carcinoma of the breast that exhibits several distinct morphologies but the link between morphology and patient outcome is not clear. We hypothesize that different mechanisms of growth may still result in similar 2D morphologies, which may look different in 3D. To elucidate the connection between growth and 3D morphology, we reconstruct the 3D architecture of cribriform DCIS from resected patient material. We produce a fully automated algorithm that aligns, segments, and reconstructs 3D architectures from microscopy images of 2D serial sections from human specimens. The alignment algorithm is based on normalized cross correlation, the segmentation algorithm uses histogram equilization, Otsu's thresholding, and morphology techniques to segment the duct and cribra. The reconstruction method combines these images in 3D. We show that two distinct 3D architectures are indeed found in samples whose 2D histological sections are similarly identified as cribriform DCIS. These differences in architecture support the hypothesis that luminal spaces may form due to different mechanisms, either isolated cell death or merging fronds, leading to the different architectures. We find that out of 15 samples, 6 were found to have 'bubble-like' cribra, 6 were found to have 'tube-like' criba and 3 were 'unknown.' We propose that the 3D architectures found, 'bubbles' and 'tubes', account for some of the heterogeneity of the disease and may be prognostic indicators of different patient outcomes.

  1. Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.

    Science.gov (United States)

    Timbrell, Simon; Al-Himdani, Sarah; Shaw, Oliver; Tan, Kian; Morris, Julie; Bundred, Nigel

    2017-04-01

    The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher. To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010. In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p = 0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins. These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.

  2. Gallbladder metastases from ductal papillary carcinoma of the breast.

    Science.gov (United States)

    Murguia, Eduardo; Quiroga, Daniel; Canteros, Geraldine; Sanmartino, Cesar; Barreiro, Mariano; Herrera, Jose

    2006-01-01

    Breast cancer occurs primarily in women aged 25 years or older. Breast carcinoma has the potential for widespread dissemination, such as metastasis to axillary lymph nodes, bone, lung, pleura, brain, and soft tissues. Liver, gastrointestinal, and biliary tract involvement are infrequent. We report a patient, a 62-year-old woman, with symptomatic cholelithiasis. The patient proceeded to laparoscopic cholecystectomy. She had a previous history of mastectomy with axillary lymphadenectomy, performed for a breast ductal papillary carcinoma, 10 years prior to the cholecystectomy. The gallbladder was hydropic; the wall was thickened, with a focal broad-based lesion on the mesenteric face of the body. Histopathological evaluation of the focal broad-based lesion of the gallbladder revealed poorly differentiated adenocarcinoma infiltration, without mucosal involvement. Subsequent immunohistochemical examination showed the lesion to be cytokeratin 7(CK7)-positive and cytokeratin 20 (CK20)-negative. Estrogen receptor (ER) and progesterone receptor (PgR) were positive. The final pathological diagnosis was breast ductal papillary carcinoma metastases to the gallbladder. Mammography of the other breast was normal. Computed tomography (CT) scan of the brain, chest, abdomen, and pelvis was performed, without any pathological findings. Bone Tc-99 scintigraphy was normal. Six months after the surgery positron emission tomography (PET) showed no evidence of metastatic disease. Two years after the surgery, the patient died, in the absence of recurrence. A literature review revealed only a few more cases of metastasic breast carcinoma to the gallbladder.

  3. E-cadherin expression in obesity-associated, Kras-initiated pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Stark, Alexander P; Chang, Hui-Hua; Jung, Xiaoman; Moro, Aune; Hertzer, Kathleen; Xu, Mu; Schmidt, Andrea; Hines, O Joe; Eibl, Guido

    2015-12-01

    The epithelial-mesenchymal transition (EMT) is critical in the development of invasive epithelial malignancies. EMT is accelerated by inflammation and results in decreased E-cadherin expression. Diet-induced obesity is an inflammatory state that accelerates pancreatic carcinogenesis; its effect on EMT and E-cadherin expression in the development of pancreatic ductal adenocarcinoma is unclear. Conditional Kras(G12D) mice were fed a control diet or a high-fat, high-calorie diet for 3 or 9 months (n = 10 each). Immunohistochemistry with anti-E-cadherin antibody was performed. E-cadherin expression was characterized by staining intensity, location, and proportion of positive cells. In vitro expression of E-cadherin and Slug in primary pancreatic intraepithelial neoplasia (PanIN) and cancer cells was determined by Western blot. The HFCD led to increased weight gain in both 3- (15.8 vs 5.6 g, P cancer, E-cadherin expression was aberrant, with loss of membranous staining and prominent cytoplasmic staining, associated with strong, cytoplasmic expression of β-catenin. In vitro expression of E-cadherin was greatest in primary PanIN cells, accompanied by absent Slug expression. Cancer cell lines demonstrated significantly decreased E-cadherin expression in the presence of upregulated Slug. Despite increased pancreatic inflammation and accelerated carcinogenesis, the high-fat, high-calorie diet did not induce changes in E-cadherin expression in PanIN lesions of all stages. Invasive lesions demonstrated aberrant cytoplasmic E-cadherin staining. Loss of normal membranous localization may reflect a functional loss of E-cadherin. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2008-01-01

    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. PMID:18479514

  5. 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.

  6. Is Sentinel Lymph Node Dissection Necessary in All Patients with Ductal Carcinoma In Situ Undergoing Total Mastectomy?

    Science.gov (United States)

    Bonev, Valentina; De Paz Villanueva, Carlos Chavez; Solomon, Naveenraj; Senthil, Maheswari; Reeves, Mark E; Garberoglio, Carlos; Lum, Sharon S

    2016-10-01

    When ductal carcinoma in situ (DCIS) is found on core needle biopsy, rates of upgrade to invasive cancer of 25 per cent and nodal positivity of 10 per cent have been reported. Sentinel lymph node dissection (SLND) is recommended when mastectomy is performed for DCIS. We investigated the role of SLND in DCIS patients undergoing partial and total mastectomy (TM). During the study period 2004 to 2013, 170 patients with DCIS were identified with a median age of 60 years (range 26-84 years). Of these, 58.2 per cent had partial mastectomy (PM) alone, 10.6 per cent had PM with SLND, and 31.1 per cent had TM with or without contralateral prophylactic mastectomy with SLND. Overall, SLND identified positive nodes in 4.2 per cent of patients. Upgrade to invasive carcinoma on final breast pathology was found in 8.2 per cent of patients overall, including 4.0 per cent of patients undergoing PM alone, 22.2 per cent undergoing PM with SLND, and 11.3 per cent for TM with SLND (P = 0.8). In this study, patients diagnosed with DCIS on core needle biopsy had lower than expected rates of positive sentinel nodes and upgrade to invasive carcinoma. Surgeons and patients should revisit the necessity of SLND in DCIS patients undergoing mastectomy, which could lead to decreased health expenditure, resources, time, morbidity, and emotional impact on patients.

  7. 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

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

    Science.gov (United States)

    2013-11-01

    centrosymmetric structure of collagen in combination with the multiphoton absorbance of laser light by the peptide bonds of collagen to act as a... Aspirin and Colorectal Cancer Incidence and Mortality by CTNNB1 Expression: A Molecular Pathological Epidemiology (MPE) Study Sun R, Nishihara R, Qian ZR...Chan AT, and Ogino S Purpose: Experimental studies showed that aspirin down-regulates theWNT/CTNNB1 (b-catenin) signaling ASPO 37th Annual Meeting

  9. Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women

    NARCIS (Netherlands)

    van der Vegt, Bert; Wesseling, J.; Pijnappel, R.M.; Dorrius, M.D.; den Heeten, G.J.; de Roos, M.A.J.; de Bock, G.H.

    There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between 'true' interval carcinomas and screen-detected/missed carcinomas hypothesising

  10. Angiotensin converting enzyme-independent, local angiotensin II-generation in human pancreatic ductal cancer tissues.

    Science.gov (United States)

    Ohta, Tetsuo; Amaya, Kohji; Yi, Shuangqin; Kitagawa, Hirohisa; Kayahara, Masato; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Nishimura, Gen-Ichi; Shimizu, Koichi; Miwa, Koichi

    2003-09-01

    Hypovascularity is an outstanding characteristic of pancreatic ductal cancer by diagnostic imaging: most pancreatic ductal cancers are hypovascular or avascular, and tumor vessels are seldom seen on angiography. However, we found that the vasculature was not always poor on angiography of surgically resected specimens of locally advanced pancreatic ductal cancers. To elucidate these controversial findings, we focused on angiotensin II, a vasoconstrictor which is directly produced from angiotensinogen at acidic pH by active trypsin. We examined whether a local angiotensin II-generating system exists in pancreatic ductal cancer tissue. We measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues from normal pancreas, pancreatic ductal cancers, colon cancers, and hepatocellular carcinomas. After surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and the Kasahara method, respectively. Tissue angiotensin II levels in pancreatic ductal cancer (n=13) were significantly higher than those of normal pancreas (n=7), colon cancers (n=7), or hepatocellular carcinomas (n=7). However, there was no significant difference in the ACE activity in tissue between them. This study provides in vivo evidence of an ACE-independent, angiotensin II-generating system in pancreatic ductal cancer tissues and suggests that locally formed angiotensin II may act on the pre-existing pancreatic arteries around the tumor, leading to formation of hypovascular or avascular regions.

  11. pH Regulatory Transporters in Pancreatic Ductal Adenocarcinoma

    DEFF Research Database (Denmark)

    Kong, Su Chii

    the expressions and functional roles of these pHregulating transporter in pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human malignancies with an overall 5-year survival rate of only 6%. Herein we focus on two pH-regulating transporter families, monocarboxylate transporters (MCTs) and V......-ATPases. MCT isoforms 1 to -4 are the only proton-coupled isoforms transporting monocarboxylates such as L-lactate. We show that MCT1 and MCT4 are robustly expressed in all PDAC cell lines studied. These transporters were found localized on the plasma membrane of PDAC cells, colocalizing with MCT chaperone...... protein basigin. Lactate influx capacity was reduced upon siRNA-mediated silencing and pharmacological inhibition of MCT1 and/or MCT4. PDAC cell migration was not significantly affected by MCT1 inhibition with AR-C155858 and MCT1 silencing, yet was inhibited by the general MCT inhibitor 4-CIN...

  12. The molecular and cellular heterogeneity of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Samuel, Nardin; Hudson, Thomas J

    2011-12-20

    Current standard therapies for pancreatic ductal adenocarcinoma have failed to attenuate the aggressiveness of this disease or confer notable improvements in survival. Previous molecular research into pancreatic cancers, along with advances in sequencing technologies, have identified many altered genes in patients with pancreatic cancer and revealed the marked genetic heterogeneity of individual tumors. Thus, the lack of success of conventional empiric therapy can be partly attributed to the underlying heterogeneity of pancreatic tumors. The genetic alterations that have been detected in pancreatic cancer range from simple mutations at the level of base pairs to complex chromosomal structural changes and rearrangements. The identification of molecular changes that are unique to an individual patient's tumors, and the subsequent development of strategies to target the tumors in a personalized approach to therapeutics, is a necessary advance to improve therapy for patients with this disease.

  13. A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis.

    Science.gov (United States)

    Raynaud, Peggy; Tate, Joshua; Callens, Céline; Cordi, Sabine; Vandersmissen, Patrick; Carpentier, Rodolphe; Sempoux, Christine; Devuyst, Olivier; Pierreux, Christophe E; Courtoy, Pierre; Dahan, Karin; Delbecque, Katty; Lepreux, Sébastien; Pontoglio, Marco; Guay-Woodford, Lisa M; Lemaigre, Frédéric P

    2011-06-01

    Ductal plate malformations (DPMs) are developmental anomalies considered to result from lack of ductal plate remodeling during bile duct morphogenesis. In mice, bile duct development is initiated by the formation of primitive ductal structures lined by two cell types, namely ductal plate cells and hepatoblasts. During ductal plate remodeling, the primitive ductal structures mature to ducts as a result from differentiation of the ductal plate cells and hepatoblasts to cholangiocytes. Here, we report this process is conserved in human fetal liver. These findings prompted us to evaluate how DPMs develop in three mouse models, namely mice with livers deficient in hepatocyte nuclear factor 6 (HNF6), HNF1β, or cystin-1 (cpk [congenital polycystic kidney] mice). Human liver from a patient with a HNF1B/TCF2 mutation, and from fetuses affected with autosomal recessive polycystic kidney disease (ARPKD) were also analyzed. Despite the epistatic relationship between HNF6, HNF1β, and cystin-1, the three mouse models displayed distinct morphogenic mechanisms of DPM. They all developed biliary cysts lined by cells with abnormal apicobasal polarity. However, the absence of HNF6 led to an early defect in ductal plate cell differentiation. In HNF1β-deficient liver, maturation of the primitive ductal structures was impaired. Normal differentiation and maturation but abnormal duct expansion was apparent in cpk mouse livers and in human fetal ARPKD. DPM is the common endpoint of distinct defects initiated at distinct stages of bile duct morphogenesis. Our observations provide a new pathogenic classification of DPM. Copyright © 2011 American Association for the Study of Liver Diseases.

  14. 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.

  15. Invasive Species

    Science.gov (United States)

    Invasive species have significantly changed the Great Lakes ecosystem. An invasive species is a plant or animal that is not native to an ecosystem, and whose introduction is likely to cause economic, human health, or environmental damage.

  16. 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.

  17. Paracrine Secretion of Transforming Growth Factor β by Ductal Cells Promotes Acinar-to-Ductal Metaplasia in Cultured Human Exocrine Pancreas Tissues.

    Science.gov (United States)

    Akanuma, Naoki; Liu, Jun; Liou, Geou-Yarh; Yin, Xue; Bejar, Kaitlyn R; Liu, Chengyang; Sun, Lu-Zhe; Storz, Peter; Wang, Pei

    2017-10-01

    We aimed to evaluate the contribution of acinar-to-ductal metaplasia (ADM) to the accumulation of cells with a ductal phenotype in cultured human exocrine pancreatic tissues and reveal the underlying mechanism. We sorted and cultured viable cell populations in human exocrine pancreatic tissues with a flow cytometry-based lineage tracing method to evaluate possible mechanisms of ADM. Cell surface markers, gene expression pattern, and sphere formation assay were used to examine ADM. A large proportion of acinar cells gained CD133 expression during the 2-dimensional culture and showed down-regulation of acinar markers and up-regulation of ductal markers, assuming an ADM phenotype. In a serum-free culture condition, ADM induction was mainly dependent on transforming growth factor β (TGF-β) secreted from cultured ductal cells. Human acinar cells when cultured alone for a week in a serum-free condition do not undergo ADM. However, serum may contain other factors besides TGF-β to induce ADM in human acinar cells. In addition, we found that TGF-β cannot induce ADM of murine acinar cells. Ductal cells are the major source of TGF-β that induces ADM in cultured human exocrine pancreatic tissues. This culture system might be a useful model to investigate the mechanism of ADM in human cells.

  18. 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

  19. Youngest case of ductal carcinoma in situ arising within a benign phyllodes tumour: A case report.

    Science.gov (United States)

    Chopra, Sharat; Muralikrishnan, Vummiti; Brotto, Maurizio

    2016-01-01

    Phyllodes tumour (PT) is a rare tumour of the female breast. The tumour clinically and radiologically mimics the features of a fibroadenoma. Ductal carcinoma in situ (DCIS) in the epithelial component of PT is a very rare finding. We present youngest ever case of a 23-year-old nulliparous woman with high-grade ductal carcinoma in situ arising within a benign phyllodes tumor. Macroscopically, it is a homogeneous tumour with solid components. Microscopically, it features typical leaf-like pattern with hypercellular stroma with high-grade ductal carcinoma in situ. To date, eight such rare cases of benign phyllodes tumour with ductal carcinoma in situ have been documented. We report the youngest case known in literature so far. As this is a very rare presentation, it poses several challenges in regard to both management and follow-up. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Systematic review of peri-operative prognostic biomarkers in pancreatic ductal adenocarcinoma

    NARCIS (Netherlands)

    Petrushnko, W.; Gundara, J.S.; Reuver, P.R.; O'Grady, G.; Samra, J.S.; Mittal, A.

    2016-01-01

    BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. METHODS: A systematic review was

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

    National Research Council Canada - National Science Library

    Griffith, Jeffrey K

    2006-01-01

    ...) that was developed and characterized by the Principal Investigator to test the hypothesis that TC can be used to predict the likelihood of disease progression in women with Ductal Carcinoma in Situ (DCIS...

  2. Ductal Carcinoma In Situ of the Breast: A Systematic Review of Incidence, Treatment, and Outcomes

    National Research Council Canada - National Science Library

    Virnig, Beth A; Tuttle, Todd M; Shamliyan, Tatyana; Kane, Robert L

    2010-01-01

    Background The National Institutes of Health Office of Medical Applications of Research commissioned a structured literature review on the incidence, treatment, and outcomes of ductal carcinoma in situ (DCIS...

  3. 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.

  4. Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells

    Science.gov (United States)

    Jimbo, Masaya; Blanco, Fernando F.; Screnci, Brad A.; Cosma, Gabriela L.; Alexeev, Vitali; Gonye, Gregory E.; Yeo, Charles J.; Sawicki, Janet A.; Winter, Jordan M.; Brody, Jonathan R.

    2015-01-01

    Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR’s role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs significantly decreased cell proliferation and anchorage-independent growth, as well as impaired migration and invasion. In comparison, HuR overexpression increased migration and invasion, but had no significant effects on cell proliferation and anchorage-independent growth. Importantly, two distinct targeted approaches to HuR silencing showed marked impairment in tumor growth in mouse xenografts. NanoString nCounter® analyses demonstrated that HuR regulates core biological processes, highlighting that HuR inhibition likely thwarts PDA viability through post-transcriptional regulation of diverse signaling pathways (e.g. cell cycle, apoptosis, DNA repair). Taken together, our study suggests that targeted inhibition of HuR may be a novel, promising approach to the treatment of PDA. PMID:26314962

  5. Human pancreatic stellate cells modulate 3D collagen alignment to promote the migration of pancreatic ductal adenocarcinoma cells.

    Science.gov (United States)

    Drifka, Cole R; Loeffler, Agnes G; Esquibel, Corinne R; Weber, Sharon M; Eliceiri, Kevin W; Kao, W John

    2016-12-01

    A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the ability for cancer cells to aggressively infiltrate and navigate through a dense stroma during the metastatic process. Key features of the PDAC stroma include an abundant population of activated pancreatic stellate cells (PSCs) and highly aligned collagen fibers; however, important questions remain regarding how collagen becomes aligned and what the biological manifestations are. To better understand how PSCs, aligned collagen, and PDAC cells might cooperate during the transition to invasion, we utilized a microchannel-based in vitro tumor model and advanced imaging technologies to recreate and examine in vivo-like heterotypic interactions. We found that PSCs participate in a collaborative process with cancer cells by orchestrating the alignment of collagen fibers that, in turn, are permissive to enhanced cell migration. Additionally, direct contact between PSCs, collagen, and PDAC cells is critical to invasion and co-migration of both cell types. This suggests PSCs may accompany and assist in navigating PDAC cells through the stromal terrain. Together, our data provides a new role for PSCs in stimulating the metastatic process and underscores the importance of collagen alignment in cancer progression.

  6. 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.

  7. Heterogeneous Chromosomal Aberrations in Intraductal Breast Lesions Adjacent to Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Michaela Aubele

    2000-01-01

    Full Text Available There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH and ductal carcinoma in situ (DCIS. In this study we applied comparative genomic hybridization (CGH to formalin‐fixed, paraffin‐embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC, to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser‐microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP‐PCR and further processed for CGH analysis.

  8. The diagnostic challenge of low-grade ductal carcinoma in situ.

    Science.gov (United States)

    Onega, Tracy; Weaver, Donald L; Frederick, Paul D; Allison, Kimberly H; Tosteson, Anna N A; Carney, Patricia A; Geller, Berta M; Longton, Gary M; Nelson, Heidi D; Oster, Natalia V; Pepe, Margaret S; Elmore, Joann G

    2017-07-01

    Diagnostic agreement among pathologists is 84% for ductal carcinoma in situ (DCIS). Studies of interpretive variation according to grade are limited. A national sample of 115 pathologists interpreted 240 breast pathology test set cases in the Breast Pathology Study and their interpretations were compared to expert consensus interpretations. We assessed agreement of pathologists' interpretations with a consensus reference diagnosis of DCIS dichotomised into low- and high-grade lesions. Generalised estimating equations were used in logistic regression models of rates of under- and over-interpretation of DCIS by grade. We evaluated 2097 independent interpretations of DCIS (512 low-grade DCIS and 1585 high-grade DCIS). Agreement with reference diagnoses was 46% (95% confidence interval [CI] 42-51) for low-grade DCIS and 83% (95% CI 81-86) for high-grade DCIS. The proportion of reference low-grade DCIS interpretations over-interpreted by pathologists (i.e. categorised as either high-grade DCIS or invasive cancer) was 23% (95% CI 19-28); 30% (95% CI 26-34) were interpreted as a lower diagnostic category (atypia or benign proliferative). Reference high-grade DCIS was under-interpreted in 14% (95% CI 12-16) of observations and only over-interpreted 3% (95% CI 2-4). Grade is a major factor when examining pathologists' variability in diagnosing DCIS, with much lower agreement for low-grade DCIS cases compared to high-grade. These findings support the hypothesis that low-grade DCIS poses a greater interpretive challenge than high-grade DCIS, which should be considered when developing DCIS management strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. KLF4 is a novel candidate tumor suppressor gene in pancreatic ductal carcinoma.

    Science.gov (United States)

    Zammarchi, Francesca; Morelli, Mariangela; Menicagli, Michele; Di Cristofano, Claudio; Zavaglia, Katia; Paolucci, Alessandra; Campani, Daniela; Aretini, Paolo; Boggi, Ugo; Mosca, Franco; Cavazzana, Andrea; Cartegni, Luca; Bevilacqua, Generoso; Mazzanti, Chiara Maria

    2011-01-01

    Ductal pancreatic carcinoma (DPC) is a deadly disease with an incidence of 9 cases in 100,000 people per year and a mortality rate close to 100%. Allelic losses in the long arm of chromosome 9 are commonly encountered in many human malignancies but no data are yet available about DPC. We screened 40 laser-microdissected DPC samples and 6 pre-invasive lesions for 9 microsatellite mapping markers of region 9q21.3 through 9q34.2. A small overlapping region of deletion, spanning 8 million base pairs, was identified between D9S127 and D9S105. Two genes, RSG3 and KLF4, mapped to 9q31.1 through 9q32, were further investigated. A highly significant association was found between KLF4 gene expression levels and genomic status. Similarly, absence of immunohistochemical expression of KLF4 protein was found in 86.8% cases of DPC (33/38). Overexpression of KLF4 in a human pancreatic carcinoma cell line induced a significant decrease in the proliferation associated with up-regulation of p21 and the down-regulation of cyclin D1. In conclusion, we identified a novel oncosuppressor region located at the 9q 31.1-3 locus that is lost in DPC at high frequency. Loss of KLF4 expression is closely related to the genomic loss, and its restoration inhibits cancer cell proliferation, suggesting a key suppressor role in pancreatic tumorigenesis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Esposito, I; Menicagli, M; Funel, N; Bergmann, F; Boggi, U; Mosca, F; Bevilacqua, G; Campani, D

    2004-06-01

    Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness. To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance. Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker. There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages. Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.

  11. High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhang L

    2016-10-01

    Full Text Available Lingfu Zhang,1 Dianrong Xiu,1 Jun Zhan,2,3 Xiaokun He,3 Limei Guo,4,5 Jilian Wang,1 Ming Tao,1 Wei Fu,1 Hongquan Zhang2,3 1Department of General Surgery, Peking University Third Hospital, 2Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, State Key Laboratory of Natural and Biomimetic Drugs, 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, 4Department of Pathology, Peking University Health Science Center, 5Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China Aims: Recent studies showed that muscarinic acetylcholine receptor 3 (M3, as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC.Materials and methods: The localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: M3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (P<0.01, more lymph node metastasis (P<0.01 as well as shorter patient overall survival (P<0.01. Morphologically, cells with high M3 expression were more frequently located at the invasive tumor front/tumor budding cells, metastatic lymph nodes and parasympathetic nerve fibers.Conclusion: High expression of M3 is a prognostic marker for PDAC. Keywords: PDAC, muscarinic acetylcholine receptor 3, M3, tumor budding, parasympathetic nerve fiber, prognosis

  12. 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.

  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. Metabolic imaging of pancreatic ductal adenocarcinoma detects altered choline metabolism.

    Science.gov (United States)

    Penet, Marie-France; Shah, Tariq; Bharti, Santosh; Krishnamachary, Balaji; Artemov, Dmitri; Mironchik, Yelena; Wildes, Flonné; Maitra, Anirban; Bhujwalla, Zaver M

    2015-01-15

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease that develops relatively symptom-free and is therefore advanced at the time of diagnosis. The absence of early symptoms and effective treatments has created a critical need for identifying and developing new noninvasive biomarkers and therapeutic targets. We investigated the metabolism of a panel of PDAC cell lines in culture and noninvasively in vivo with (1)H magnetic resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and uncover potential metabolic targets. We observed elevated choline-containing compounds in the PDAC cell lines and tumors. These elevated choline-containing compounds were easily detected by increased total choline (tCho) in vivo, in spectroscopic images obtained from tumors. Principal component analysis of the spectral data identified additional differences in metabolites between immortalized human pancreatic cells and neoplastic PDAC cells. Molecular characterization revealed overexpression of choline kinase (Chk)-α, choline transporter 1 (CHT1), and choline transporter-like protein 1 (CTL1) in the PDAC cell lines and tumors. Collectively, these data identify new metabolic characteristics of PDAC and reveal potential metabolic targets. Total choline detected with (1)H MRSI may provide an intrinsic, imaging probe-independent biomarker to complement existing techniques in detecting PDAC. The expression of Chk-α, CHT1, and CTL1 may provide additional molecular markers in aspirated cytological samples. ©2014 American Association for Cancer Research.

  15. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Kimberly A Kelly

    2008-04-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries an extremely poor prognosis, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. The development of molecular markers and imaging probes for incipient PDAC would enable earlier detection and guide the development of interventive therapies. Here we sought to identify novel molecular markers and to test their potential as targeted imaging agents.Here, a phage display approach was used in a mouse model of PDAC to screen for peptides that specifically bind to cell surface antigens on PDAC cells. These screens yielded a motif that distinguishes PDAC cells from normal pancreatic duct cells in vitro, which, upon proteomics analysis, identified plectin-1 as a novel biomarker of PDAC. To assess their utility for in vivo imaging, the plectin-1 targeted peptides (PTP were conjugated to magnetofluorescent nanoparticles. In conjunction with intravital confocal microscopy and MRI, these nanoparticles enabled detection of small PDAC and precursor lesions in engineered mouse models.Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.

  16. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Suhane, Sonal [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Berel, Dror [Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States); Ramanujan, V. Krishnan, E-mail: Ramanujanv@csmc.edu [Metabolic Photonics Laboratory, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048 (United States)

    2011-09-09

    Highlights: {yields} We monitored mitochondrial NDUFS3 expression in clinical breast cancer specimens. {yields} NDUFS3 expression is significantly higher in highly invasive cancer specimens. {yields} Increased NDUFS3 expression correlates with tumor nuclear grade. {yields} NDUFS3 expression in invasive ductal carcinoma is a potential hypoxia marker. -- Abstract: We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

  17. Androgen and oestrogen receptors as potential prognostic markers for patients with ductal carcinoma in situ treated with surgery and radiotherapy.

    Science.gov (United States)

    Ravaioli, Sara; Tumedei, Maria Maddalena; Foca, Flavia; Maltoni, Roberta; Rocca, Andrea; Massa, Ilaria; Pietri, Elisabetta; Bravaccini, Sara

    2017-11-28

    Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has been investigated less extensively than invasive breast cancer. Women with DCIS are mainly treated with conservative surgery almost exclusively followed by radiotherapy. However, as radiation treatment is not always effective, the search for biomarkers capable of identifying DCIS lesions that could progress to invasive cancer is ongoing. Although conventional biomarkers have been thoroughly studied in invasive tumours, little is known about the role played by androgen receptor (AR), widely expressed in DCIS. A series of 42 DCIS patients treated with quadrantectomy and radiotherapy were followed for a period of up to 95 months. Of these, 11 had recurrent DCIS or progressed to invasive cancer. All tumours were analysed for clinical pathological features. Conventional biomarkers and androgen receptor expression were determined by immunohistochemistry. Our results showed that AR was higher in tumours of relapsed patients than non-relapsed patients (P value: 0.0005). Conversely, oestrogen receptor (ER) was higher, albeit not significantly, in non-relapsed patients than in relapsed patients. AR/ER ratio was considerably different in the two subgroups (P value: 0.0033). Area under the curve (AUC) values were 0.85 for AR and 0.80 for the AR/ER ratio. These preliminary results highlight the potentially important role of both AR and the AR/ER ratio as prognostic markers in DCIS. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma.

    Science.gov (United States)

    Garman, Katherine S; Kruger, Leandi; Thomas, Samantha; Swiderska-Syn, Marzena; Moser, Barry K; Diehl, Anna Mae; McCall, Shannon J

    2015-12-01

    Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individuals with and without oesophageal adenocarcinoma (EAC). We performed histological assessment of 343 unique ESMGs from 30 control patients, 24 patients with treatment-naïve high-grade columnar dysplasia (HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist assessed haematoxylin and eosin-stained ESMG images by using a scoring system that assigns individual ESMG acini to five histological types (mucous, serous, oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%) (P = 0.006). We also identified greater proportions of acini with dilation (21.9%, P metaplasia (4.3%, P = 0.001) in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to occur in areas of mucosal ulceration or tumour. We found a clear association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative progenitor cells, these associations could have significance for understanding the pathogenesis of EAC. © 2015 John Wiley & Sons Ltd.

  2. Invasive species

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is a summary of management activities and research related to invasive species on Neal Smith National Wildlife Refuge between 1992 and 2009. As part of the...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics

    Directory of Open Access Journals (Sweden)

    Ozhan Ocal

    2015-10-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48Cre;LSL-KrasG12D;Cdkn2af/f mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR signaling activates Kras. Regulators of G-protein signaling (RGS proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a KrasG12D-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane plus inhibitors of Axl signaling

  6. Analyzing miRNAs in ductal adenocarcinomas of the pancreas.

    Science.gov (United States)

    Mees, Soeren Torge; Schleicher, Christina; Mardin, Wolf Arif; Senninger, Norbert; Colombo-Benkmann, Mario; Haier, Joerg

    2011-08-01

    MicroRNAs (miRNAs) have gained attention as an epigenetic component involved in the development of pancreatic ductal adenocarcinoma (PDAC). Several methods for miRNA profiling are in common use, but the validity of these methods is not defined. The aim of this study was to define the optimal method for miRNA detection in PDAC. miRNA expression was determined using different and partially redundant methods (miRNA microarray, TaqMan low density array (TLDA), single tube quantitative RT-PCR). The data from different methods were statistically evaluated and tested for intermethodic consistency and reliability of the results. Finally, the miRNA expression status and the cell lines' ability to metastasize were correlated. Comparing low and high metastatic cells, miRNA-microarrays identified fewer differentially expressed and only upregulated miRNAs (n=27; 27 up-regulated) compared with TLDAs (n=54; 19 up- and 35 down-regulated). Evaluating miRNAs that target tumor suppressor genes, expression of all single tube quantitative real-time reverse transcriptase PCR (qRT-PCR) validated miRNAs was detected to be significantly altered in TLDA analysis (100%). MiRNA microarrays detected only 25% of qRT-PCR validated miRNAs. Furthermore, results from TLDA analysis correlated well with data from qRT-PCR and presented ΔΔCt values from 3.5±1.86 (range 0.8-5.62) compared with 3.74±1.86 (range 0.78-5.95) in qRT-PCR. Notable differences comparing data obtained from different screening methods were found. While TLDA and qRT-PCR correlated well in quantity and quality of the measured miRNAs, several tumor suppressor gene targeting and down-regulated miRNAs were not detected by miRNA-microarrays. This heterogeneity shows that care must be exercised when comparing results from different methods in PDAC. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Characterization of pancreatic ductal cells in human islet preparations.

    Science.gov (United States)

    Ichii, Hirohito; Miki, Atsushi; Yamamoto, Toshiyuki; Molano, Ruth D; Barker, Scott; Mita, Atsuyoshi; Rodriguez-Diaz, Rayner; Klein, Dagmar; Pastori, Ricardo; Alejandro, Rodolfo; Inverardi, Luca; Pileggi, Antonello; Ricordi, Camillo

    2008-11-01

    Substantial amounts of nonendocrine cells are implanted as part of human islet grafts, and a possible influence of nonendocrine cells on clinical islet transplantation outcome has been postulated. There are currently no product release criteria specific for nonendocrine cells due to lack of available methods. The aims of this study were to develop a method for the evaluation of pancreatic ductal cells (PDCs) for clinical islet transplantation and to characterize them regarding phenotype, viability, and function. We assessed 161 human islet preparations using laser scanning cytometry (LSC/iCys) for phenotypic analysis of nonendocrine cells and flow cytometry (FACS) for PDC viability. PDC and beta-cells obtained from different density fractions during the islet cell purification were compared in terms of viability. Furthermore, we examined PDC ability to produce proinflammatory cytokines/chemokines, vascular endothelial growth factor (VEGF) and tissue factor (TF) relevant to islet graft outcome. Phenotypic analysis by LSC/iCys indicated that single staining for CK19 or CA19-9 was not enough for identifying PDCs, and that double staining for amylase and CK19 or CA19-9 allowed for quantitative evaluation of acinar cells and PDC content in human islet preparation. PDC showed a significantly higher viability than beta-cells (PDC vs beta-cell: 75.5+/-13.9 and 62.7+/-18.7%; P<0.0001). Although beta-cell viability was independent of its density, that of PDCs was higher as the density from which they were recovered increased. There was no correlation between PDCs and beta-cell viability (R(2)=0.0078). PDCs sorted from high-density fractions produced significantly higher amounts of proinflammatory mediators and VEGF, but not TF. We conclude that PDCs isolated from different fractions had different viability and functions. The precise characterization and assessment of these cells in addition to beta-cells in human islet cell products may be of assistance in understanding

  8. Intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia is a risk factor for the subsequent development of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Rezaee, Neda; Barbon, Carlotta; Zaki, Ahmed; He, Jin; Salman, Bulent; Hruban, Ralph H; Cameron, John L; Herman, Joseph M; Ahuja, Nita; Lennon, Anne Marie; Weiss, Matthew J; Wood, Laura D; Wolfgang, Christopher L

    2016-03-01

    Non-invasive intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and IPMN-associated invasive pancreatic ductal adenocarcinoma (PDAC) are frequently included under the term "malignancy". The goal of this study is to clarify the difference between these two entities. From 1996 to 2013, data of 616 patients who underwent pancreatic resection for an IPMN were reviewed. The median overall survival for patients with IPMN with high-grade dysplasia (92 months) was similar to survival for patients with IPMN with low/intermediate-grade dysplasia (118 months, p = 0.081), and superior to that of patients with IPMN-associated PDAC (29 months, p < 0.001). IPMN-associated PDAC had lymph node metastasis in 53%, perineural invasion in 58%, and vascular invasion in 33%. In contrast, no lymph node metastasis, perineural or vascular invasion was observed with high-grade dysplasia. None of the patients with IPMN with high-grade dysplasia developed recurrence outside the remnant pancreas. In stark contrast 58% of patients with IPMN-associated PDAC recurred outside the remnant pancreas. The rate of progression within the remnant pancreas was significant in patients with IPMN with high-grade (24%) and with low/intermediate dysplasia (22%, p = 0.816). Non-invasive IPMN with high-grade dysplasia should not be considered a malignant entity. Compared to patients with IPMN with low/intermediate-grade dysplasia, those with high-grade dysplasia have an increased risk of subsequent development of PDAC in the remnant pancreas. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. Diagnosis of ductal carcinoma in situ using contrast-enhanced magnetic resonance mammography compared with conventional mammography.

    Science.gov (United States)

    Vag, Tibor; Baltzer, Pascal A T; Renz, Diane M; Pfleiderer, Stefan O R; Gajda, Mieczyslaw; Camara, Oumar; Kaiser, Werner A

    2008-01-01

    The objective of this study is to compare mammography with magnetic resonance mammography (MRM) in the diagnosis of histopathologically verified subtypes of ductal carcinoma in situ (DCIS). All patients with verified pure DCIS lesions (no signs of invasion or microinvasion) after surgery were identified between 2004 and 2006. Selection criteria were performed mammography and MRM at our institute prior to surgery resulting in a cohort of 33 patients (mean patient age, 60 years; mean lesion size, 15 mm). Magnetic resonance mammography enabled identification of DCIS in 29 of 33 patients with histopathologically verified pure DCIS (7 G1, 13 G2, and 9 G3 subtypes), giving an overall sensitivity of 87.9% for this patient cohort. Four DCIS lesions (two G1 and two G2) up to 5 mm diameter or smaller were not detected by MRM. In mammography, 21 of the 33 patients revealed suspicious outcome (including all lesions not detected by MRM), demonstrating an overall sensitivity of 63.6%. The remaining 12 mammographically occult DCIS lesions (three G1 subtypes, four G2 subtypes, five G3 subtypes) were all identified in MRM. Magnetic resonance mammography can diagnose mammographically visible and also occult DCIS lesions without microcalcifications. Only small DCIS foci with microcalcifications could additionally be verified by mammography supposing MRM as a diagnostic approach.

  11. Protocol for Biomarker Ratio Imaging Microscopy with Specific Application to Ductal Carcinoma in Situ of the Breast

    Directory of Open Access Journals (Sweden)

    Howard Raymond Petty

    2016-11-01

    Full Text Available This protocol describes the methods and steps involved in performing biomarker ratio imaging microscopy (BRIM using formalin fixed paraffin-embedded (FFPE samples of human breast tissue. The technique is based on the acquisition of two fluorescence images of the same microscopic field using two biomarkers and immunochemical tools. The biomarkers are selected such that one biomarker correlates with breast cancer aggressiveness while the second biomarker anti-correlates with aggressiveness. When the former image is divided by the latter image, a computed ratio image is formed that reflects the aggressiveness of tumor cells while increasing contrast and eliminating path-length and other artifacts from the image. For example, the aggressiveness of epithelial cells may be assessed by computing ratio images from N-cadherin and E-cadherin images or CD44 and CD24 images. These ratio micrographs reveal the mesenchymal or stem cell nature of the constituent cells, respectively. This methodology is illustrated for tissue samples of ductal carcinoma in situ (DCIS and invasive breast cancer. This tool should be useful in tissue studies of experimental cancer as well as the management of cancer patients.

  12. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

    Science.gov (United States)

    Saloman, Jami L; Albers, Kathryn M; Li, Dongjun; Hartman, Douglas J; Crawford, Howard C; Muha, Emily A; Rhim, Andrew D; Davis, Brian M

    2016-03-15

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

  13. FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis.

    Science.gov (United States)

    Sizemore, Gina M; Sizemore, Steven T; Pal, Bhupinder; Booth, Christine N; Seachrist, Darcie D; Abdul-Karim, Fadi W; Kume, Tsutomu; Keri, Ruth A

    2013-07-01

    Expression of FOXC1, a forkhead box transcription factor, correlates with the human basal-like breast cancer (BLBC) subtype, and functional analyses have revealed its importance for in vitro invasiveness of BLBC cells. Women diagnosed with this breast tumor subtype have a poorer outcome because of the lack of targeted therapies; thus, continued investigation of factors driving these tumors is critical to uncover novel therapeutic targets. Several processes that dictate normal mammary morphogenesis parallel cancer progression, and enforced expression of FOXC1 can induce a progenitor state in more-differentiated mammary epithelial cells. Consequently, evaluating how FOXC1 functions in the normal gland is critical to further understand BLBC biology. Although FOXC1 is well known to control normal development of a number of tissues, its role in the mammary gland has not yet been investigated. Herein, we describe FOXC1 expression patterning in the normal breast, where it is localized to the basal/myoepithelium, suggesting that FOXC1 would be required for normal development. However, mammary glands lacking Foxc1 have no overt defect in ductal outgrowth, alveologenesis, or lineage specification. Of significant interest, we found that expression of FOXC1 is enriched in the normal luminal progenitor population, which is the postulated cell of origin of BLBC. These results indicate that FOXC1 is unnecessary for mammary morphogenesis and that its role in BLBC likely involves processes that are unrelated to cell lineage specification.

  14. IL-8-Positive Tumor-Infiltrating Inflammatory Cells Are a Novel Prognostic Marker in Pancreatic Ductal Adenocarcinoma Patients.

    Science.gov (United States)

    Fang, Yuan; Saiyin, Hexige; Zhao, Xinping; Wu, Yanhua; Han, Xu; Lou, Wenhui

    2016-01-01

    Tumor-infiltrating inflammatory cells (TIICs) in pancreatic ductal adenocarcinoma (PDAC) are reported to initiate and exacerbate invasion and metastasis. Interleukin-8 (IL-8), a proinflammatory cytokine, is expressed in both neoplastic cells and TIICs in PDAC tissues and increased in patient serum. The aim of this study is to evaluate the values of IL-8 expression profiles in tumor tissues and predict the source of serum IL-8 in PDAC patients. We used 2 independent groups of PDAC patient samples that included 240 cases. Tissue expression profiles of cytokines were evaluated with immunohistochemistry and serum levels with human IL-8 assay. The prognostic values of the variables were assessed by Kaplan-Meier or Cox regression analysis. Higher levels of IL-8-positive TIICs but not tumor cells in PDAC patients correlated with worse prognosis (P = 0.009) and higher blood serum IL-8 levels (P = 0.002). Controlling other independent factors, the relative hazard ratio for PDAC with higher IL-8-positive TIIC levels compared with those with lower TIIC levels was 1.588 (95% confidence interval, 1.04-2.42). Higher IL-8-positive TIIC levels in PDAC tumors indicate poorer prognosis and positively correlate with serum IL-8 concentrations and vice versa. These data suggested that IL-8 might have a potential target for PDAC therapies.

  15. 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

  16. Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer.

    Science.gov (United States)

    Pundavela, Jay; Roselli, Severine; Faulkner, Sam; Attia, John; Scott, Rodney J; Thorne, Rick F; Forbes, John F; Bradshaw, Ralph A; Walker, Marjorie M; Jobling, Phillip; Hondermarck, Hubert

    2015-10-01

    Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. High Prevalence of MRI-Detected Contralateral and Ipsilateral Malignant Findings in Patients With Invasive Ductolobular Breast Cancer : Impact on Surgical Management

    NARCIS (Netherlands)

    El Sharouni, Mary Ann; Postma, Emily L; Menezes, Gisela L G|info:eu-repo/dai/nl/413920763; van den Bosch, Maurice A A J|info:eu-repo/dai/nl/182981630; Pijnappel, Ruud M.|info:eu-repo/dai/nl/239429583; Witkamp, Arjen J.|info:eu-repo/dai/nl/245008780; van der Pol, Carmen C.|info:eu-repo/dai/nl/41397006X; Verkooijen, Helena M.|info:eu-repo/dai/nl/213707705; van Diest, Paul J.|info:eu-repo/dai/nl/075281775

    2016-01-01

    INTRODUCTION: Invasive breast cancer comprises a spectrum of histologic changes with purely lobular and purely ductal cancer on either side and mixed lesions in between. Our aim was to evaluate to what extent preoperative magnetic resonance imaging (MRI) leads to the finding of additional

  18. Prognostic Value of Resection Margin Involvement After Pancreaticoduodenectomy for Ductal Adenocarcinoma: Updates From a French Prospective Multicenter Study.

    Science.gov (United States)

    Delpero, Jean Robert; Jeune, Florence; Bachellier, Philippe; Regenet, Nicolas; Le Treut, Yves Patrice; Paye, Francois; Carrere, Nicolas; Sauvanet, Alain; Adham, Mustapha; Autret, Aurelie; Poizat, Flora; Turrini, Olivier; Boher, Jean Marie

    2017-11-01

    The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma. The definition and prognostic value of incomplete microscopic resection (R1) remain controversial. Prognostic factors were analyzed in 147 patients included in a prospective multicenter study on the impact of tumor clearance evaluated using a standardized pathology protocol. Thirty patients received neoadjuvant treatment (NAT = 20%); 41 had venous resection (VR = 28%), and 70% received adjuvant chemotherapy. In-hospital mortality was 3% (5/147). Follow-up was 83 months. Tumor clearance was 0, status from R1-direct invasion (0 mm) to R1 <1.0 mm. On univariate analysis, clearance <1.0 or <1.5 mm, pT stage, pN stage, LNR ≥0.2, tumor grade 3, and lymphovascular invasion were significantly associated with 5-year survival. On multivariate analysis, pN was the most powerful independent predictor (P = 0.004). Clearance <1.0 or <1.5 mm had borderline significance for the entire cohort, but was relevant in certain subgroups (upfront pancreatectomy (n = 117; P = 0.049); without VR or NAT (n = 87; P = 0.003); N+ without VR or NAT (n = 50; P = 0.004). No N0-patient had R1-0 mm. Additional independent risk predictors were (1) R1 <1.0 mm for the SMA-margin in specific subgroups (upfront pancreatectomy, N0 patients without NAT, N+ patients without NAT or VR; (2) R1-0 mm posterior-margin for the NAT group (P = 0.004). Tumor clearance <1.0 or <1.5 mm was an independent determinants of postresection survival in certain subgroups. To avoid misinterpretation, future trials should specify the clearance margin in millimeter. ClinicalTrials.gov: NCT00918853.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Soo Yeon; Han, Boo-Kyung; Ko, Eun Young; Shin, Jung Hee; Nam, Meeyoung [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of)], e-mail: bkhan@skku.edu; Hwang, Ji-Young [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym Univ. Coll. of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    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, {chi}{sup 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

  20. The florid subtype of lobular carcinoma in situ: marker or precursor for invasive lobular carcinoma?

    Science.gov (United States)

    Bagaria, Sanjay P; Shamonki, Jaime; Kinnaird, Michelle; Ray, Partha S; Giuliano, Armando E

    2011-07-01

    Lobular carcinoma in situ (LCIS) is considered a risk factor-not a precursor-for both invasive lobular and ductal carcinoma. Florid LCIS (F-LCIS) is an architectural subtype of LCIS that does not express E-cadherin, yet has the histologic and often radiographic appearance of solid-type ductal carcinoma in situ (DCIS). Since DCIS is considered a precursor to invasive ductal carcinoma, should F-LCIS be considered a precursor to invasive lobular carcinoma (ILC)? Review of an institutional database identified cases of LCIS and solid-type DCIS diagnosed by excisional biopsy, segmentectomy, or mastectomy between 1991 and 2000 to determine the prevalence of associated invasive breast cancer. Archival specimens were evaluated for florid and nonflorid LCIS, nuclear grade of LCIS, and the presence and subtype of invasive breast cancer. Solid-type DCIS that lacked E-cadherin expression was classified as F-LCIS. Of 210 consecutive specimens of LCIS examined, 171 had nonflorid LCIS (81%) and 39 had F-LCIS (19%). Nonflorid LCIS had a diffuse pattern, whereas F-LCIS appeared as discrete foci adjacent to ILC. An invasive component was identified with 87% of F-LCIS lesions versus 73% of nonflorid LCIS lesions (P = 0.064); this component was lobular in 100% of F-LCIS lesions versus 82% of nonflorid LCIS lesions, a significant difference (P = 0.0044) that persisted when the analysis was adjusted for nuclear grade (P = 0.0082). Its close spatial relationship to an invasive component and increased association with ILC suggest that F-LCIS may be a precursor for ILC.

  1. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    OpenAIRE

    Prionas, Nicolas D.; Aminololama-Shakeri, Shadi; Yang, Kai; Martinez, Steve R.; Lindfors, Karen K.; Boone, John M.

    2015-01-01

    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 obta...

  2. 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 ...

  3. Glucose Uptake and Intracellular pH in a Mouse Model of Ductal Carcinoma In Situ (DCIS Suggests Metabolic Heterogeneity

    Directory of Open Access Journals (Sweden)

    Rebecca C. Lobo

    2016-08-01

    Full Text Available Mechanisms for the progression of ductal carcinoma in situ (DCIS to invasive breast carcinoma remain unclear. Previously we showed that the transition to invasiveness in the mammary intraepithelial neoplastic outgrowth (MINO model of DCIS does not correlate with its serial acquisition of genetic mutations. We hypothesized instead that progression to invasiveness depends on a change in the microenvironment and that precancer cells might create a more tumor-permissive microenvironment secondary to changes in glucose uptake and metabolism. Immunostaining for glucose transporter 1 (GLUT1 and the hypoxia marker carbonic anhydrase 9 (CAIX in tumor, normal mammary gland and MINO (precancer tissue showed differences in expression. The uptake of the fluorescent glucose analog dye, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl amino]-2-deoxy-D-glucose (2-NBDG, reflected differences in the cellular distributions of glucose uptake in normal mammary epithelial cells (nMEC, MINO and Met1 cancer cells, with a broad distribution in the MINO population. The intracellular pH (pHi measured using the fluorescent ratio dye 2’,7’-bis(2-carboxyethyl-5(6-155 carboxyfluorescein-AM (BCECF-AM revealed expected differences between normal and cancer cells (low and high, respectively, and a mixed distribution in the MINO cells, with a subset of cells in the MINO having an increased rate of acidification when proton efflux was inhibited. Invasive tumor cells had a more alkaline baseline pHi with high rates of proton production coupled with higher rates of proton export, compared with nMEC. MINO cells displayed considerable variation in baseline pHi that separated into two distinct populations: MINO high and MINO low. MINO high had a noticeably higher mean acidification rate compared with nMEC, but relatively high baseline pHi similar to tumor cells. MINO low cells also had an increased acidification rate compared with nMEC, but with a more acidic pHi similar to nMEC. These

  4. 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

  5. CI- and K+ Channels in Pancreatic Ductal Adenocarcinoma (PDAC)

    DEFF Research Database (Denmark)

    Sauter, Daniel Rafael Peter

    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...

  6. PD2/Paf1 depletion in pancreatic acinar cells promotes acinar-to-ductal metaplasia.

    Science.gov (United States)

    Dey, Parama; Rachagani, Satyanarayana; Vaz, Arokia P; Ponnusamy, Moorthy P; Batra, Surinder K

    2014-06-30

    Pancreatic differentiation 2 (PD2), a PAF (RNA Polymerase II Associated Factor) complex subunit, is overexpressed in pancreatic cancer cells and has demonstrated potential oncogenic property. Here, we report that PD2/Paf1 expression was restricted to acinar cells in the normal murine pancreas, but its expression increased in the ductal cells of KrasG12D/Pdx1Cre (KC) mouse model of pancreatic cancer with increasing age, showing highest expression in neoplastic ductal cells of 50 weeks old mice. PD2/Paf1 was specifically expressed in amylase and CK19 double positive metaplastic ducts, representing intermediate structures during pancreatic acinar-to-ductal metaplasia (ADM). Similar PD2/Paf1 expression was observed in murine pancreas that exhibited ADM-like histology upon cerulein challenge. In normal mice, cerulein-mediated inflammation induced a decrease in PD2/Paf1 expression, which was later restored upon recovery of the pancreatic parenchyma. In KC mice, however, PD2/Paf1 mRNA level continued to decrease with progressive dysplasia and subsequent neoplastic transformation. Additionally, knockdown of PD2/Paf1 in pancreatic acinar cells resulted in the abrogation of Amylase, Elastase and Lipase (acinar marker) mRNA levels with simultaneous increase in CK19 and CAII (ductal marker) transcripts. In conclusion, our studies indicate loss of PD2/Paf1 expression during acinar transdifferentiation in pancreatic cancer initiation and PD2/Paf1 mediated regulation of lineage specific markers.

  7. Outcomes of Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma in the Netherlands: A Nationwide Retrospective Analysis

    NARCIS (Netherlands)

    Rooij, T. de; Tol, J.A.; Eijck, C.H. van; Boerma, D.; Bonsing, B.A.; Bosscha, K.; Dam, R.M. van; Dijkgraaf, M.G.; Gerhards, M.F.; Goor, H. van; Harst, E. van der; Hingh, I.H. de; Kazemier, G.; Klaase, J.M.; Molenaar, I.Q.; Patijn, G.A.; Santvoort, H.C. van; Scheepers, J.J.; Schelling, G.P. van der; Sieders, E.; Busch, O.R.; Besselink, M.G.

    2016-01-01

    BACKGROUND: Large multicenter series on outcomes and predictors of survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC) are scarce. METHODS: Adults who underwent DP for PDAC in 17 Dutch pancreatic centers between January 2005 and September 2013 were analyzed

  8. Outcomes of Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma in the Netherlands: A Nationwide Retrospective Analysis

    NARCIS (Netherlands)

    T. de Rooij (Thijs); J.A. Tol (Johanna A.); C.H.J. van Eijck (Casper); D. Boerma (Djamila); B.A. Bonsing (Bert); K. Bosscha (Koop); R. van Dam (Ronald); M.G.W. Dijkgraaf (Marcel); M.F. Gerhards (Michael); H. van Goor (Harry); E. van der Harst (Erwin); I.H.J.T. de Hingh (Ignace); G. Kazemier (Geert); J.M. Klaase (Joost); I.Q. Molenaar (I. Quintus); G.A. Patijn (Gijs A.); H.C. van Santvoort (Hjalmar); J.J. Scheepers (Joris J.); G. van der Schelling; E. Sieders (Egbert); O.R.C. Busch (Olivier); M.G. Besselink (Marc)

    2016-01-01

    textabstractBackground: Large multicenter series on outcomes and predictors of survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC) are scarce. Methods: Adults who underwent DP for PDAC in 17 Dutch pancreatic centers between January 2005 and September 2013 were

  9. Variation in detection of ductal carcinoma in situ during screening mammography

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Ponti, Antonio; James, Ted

    2014-01-01

    BACKGROUND: There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative...

  10. Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    Correa, C.; McGale, P.; Taylor, C.; Wang, Y.; Clarke, M.; Davies, C.; Peto, R.; Bijker, N.; Solin, L.; Darby, S.; Abe, O.; Abe, R.; Enomoto, K.; Kikuchi, K.; Koyama, H.; Masuda, H.; Nomura, Y.; Ohashi, Y.; Sakai, K.; Sugimachi, K.; Toi, M.; Tominaga, T.; Uchino, J.; Yoshida, M.; Haybittle, J. L.; Leonard, C. F.; Calais, G.; Geraud, P.; Collett, V.; Delmestri, A.; Sayer, J.; Harvey, V. J.; Holdaway, T. M.; Kay, R. G.; Mason, B. H.; Forbes, J. F.; Wilcken, N.; Bauernhofer, T.; Dubsky, P.; Fesl, C.; Fohler, H.; Filipcic, L.; Filipits, M.; Fridrik, M.; Gnant, M.; Greil, R.; Hegenbarth, K.; Jakesz, R.; Kwasny, W.; Lang, A.; Luschin-Ebengreuth, G.; Marth, C.; Menzel, C.; Mlineritsch, B.; Samonigg, H.; Seifert, M.; Sevelda, P.; Singer, C.; Steger, G. G.; Stöger, H.; Thaler, J.; Tschmelitsch, J.; Zielinski, C.; Canney, P.; Yosef, H. M. A.; Focan, C.; Peek, U.; Oates, G. D.; Powell, J.; Durand, M.; Mauriac, L.; Di Leo, A.; Dolci, S.; Piccart, M. J.; Masood, M. B.; Parker, D.; Price, J. J.; Lindsay, M. A.; Mackey, J.; Martin, M.; Hupperets, P. S. G. J.; Bates, T.; Blamey, R. W.; Chetty, U.; Ellis, I. O.; Mallon, E.; Morgan, D. A. L.; Patnick, J.; Pinder, S.; Jackson, S.; Ragaz, J.; Berry, D.; Broadwater, G.; Cirrincione, C.; Muss, H.; Norto, L.; Weiss, R. B.; Abu-Zahra, H. T.; Portnoj, S. M.; Baum, M.; Cuzick, J.; Dowsett, M.; Houghton, J.; Ledermann, J.; Riley, D.; Bowdon, S.; Brookes, C.; Fernando, I.; Rea, D.; Spooner, D.; Mansel, R. E.; Gordon, N. H.; Davis, H. L.; Lehingue, Y.; Romestaing, P.; Dubois, J. B.; Delozier, T.; Griffon, B.; Mace Lesec'h, J.; Rambert, P.; Mustacchi, G.; Petruzelka, L.; Pribylova, O.; Owen, J. R.; Harbeck, N.; Jänicke, F.; Meisner, C.; Schmitt, M.; Thomssen, C.; Meier, P.; Howell, A.; Swindell, R.; Burrett, J.; Collins, R.; Cutter, D.; Davies, K.; Elphinstone, P.; Evans, V.; Gettins, L.; GodwinF, J.; Gray, R.; Gregory, C.; Hermans, D.; Hicks, C.; James, S.; Kerr, A.; MacKinnon, E.; Lay, M.; McHugh, T.; Albano, J.; de Oliveira, C. F.; Gervásio, H.; Gordilho, J.; Johansen, H.; Mouridsen, H. T.; Gelman, R. S.; Harris, J. R.; Hayes, D.; Henderson, I. C.; Shapiro, C. L.; Winer, E.; Christiansen, P.; Ejlertsen, B.; Ewertz, M.; Møller, S.; Overgaard, M.; Carstensen, B.; Palshof, T.; Trampisch, H. J.; Dalesio, O.; de Vries, E. G. E.; Rodenhuis, S.; van Tinteren, H.; ComisF, R. L.; DavidsonF, N. E.; Robert, N.; SledgeF, G.; Solin, F. J.; Tormey, D. C.; Wood, W.; Cameron, D.; Forrest, P.; Jack, W.; Rossbach, J.; Klijn, J. G. M.; Treurniet-Donker, A. D.; van Putten, W. L. J.; Costa, A.; Veronesi, U.; Viale, G.; Bartelink, H.; Bogaerts, J.; Julien, J. P.; Legrand, C.; Rutgers, E.; Sylvester, R.; van de Velde, C. J. H.; van Nes, J. G. H.; Cunningham, M. P.; Huovinen, R.; Joensuu, H.; Tinterri, C.; Valagussa, P.; Goldstein, L. J.; Bonneterre, J.; Fargeot, P.; Fumoleau, P.; Kerbrat, P.; Luporsi, E.; Namer, M.; Eiermann, W.; Hilfrich, J.; Jonat, W.; Kaufmann, M.; KreienbergF, R.; Schumacher, M.; Bastert, G.; Rauschecker, H.; Sauer, R.; Sauerbrei, W.; Schauer, A.; Blohmer, J. U.; Costa, S. D.; Eidtmann, H.; Gerber, B.; Jackisch, C.; Loibl, S.; von Minckwitz, G.; de Schryver, A.; Vakaet, L.; Belfiglio, M.; Nicolucci, A.; Pellegrini, F.; Sacco, M.; Valentini, M.; McArdle, C. S.; Smith, D. C.; Stallard, S.; Galligioni, E.; Lopez, M.; Boccardo, F.; Rubagotti, A.; Dent, D. M.; Gudgeon, C. A.; Hacking, A.; Murray, E.; Panieri, E.; Briones, L.; Carrasco, E.; Erazo, A.; Medina, J. Y.; Horiguchi, J.; Takei, H.; Fentiman, I. S.; Hayward, J. L.; Rubens, R. D.; Skilton, D.; Scheurlen, H.; Sohn, H. C.; Untch, M.; Dafni, U.; Markopoulos, C.; Fountzilas, G.; Mavroudis, D.; Klefstrom, P.; Blomqvist, C.; Saarto, C.; Gallen, M.; Margreiter, R.; de Lafontan, B.; Mihura, J.; RochéF, H.; Asselain, B.; Salmon, R. J.; Vilcoq, J. R.; Arriagada, R.; Hill, C.; Laplanche, A.; Lê, M. G.; Spielmann, M.; A'Hern, R.; Barrett-Lee, P.; Bliss, J.; Ellis, P.; Kilburn, L.; Yarnold, J. R.; Bruzzi, P.; del Mastro, L.; Pronzato, P.; Sertoli, M. R.; Venturini, M.; Amadori, D.; Benraadt, J.; Kooi, M.; van de Velde, A. O.; van Dongen, J. A.; Vermorken, J. B.; Castiglione, M.; Cavalli, F.; Coates, A.; Collins, J.; Forbes, J.; Gelber, R. D.; Goldhirsch, A.; Lindtner, J.; Price, K. N.; Raina, V.; Rudenstam, C. M.; Senn, H. J.; Bliss, J. M.; Chilvers, C. E. D.; Coombes, R. C.; Hall, E.; Marty, M.; Buyse, M.; Possinger, K.; Schmid, P.; Wallwiener, D.; Borovik, R.; Brufman, G.; Hayat, H.; Robinson, E.; Yaal-Hahoshen, N.; Bonadonna, G.; Camerini, T.; de Palo, G.; Di MauroF, M. G.; Formelli, F.; Martoni, A.; Pannuti, F.; Cocconi, G.; Colozza, A.; Camisa, R.; Gori, S.; Aogi, K.; Takashima, S.; Ikeda, T.; Inokuchi, K.; Sawa, K.; Sonoo, H.; Korzeniowski, S.; Skolyszewski, J.; Ogawa, M.; Yamashita, J.; Christiaens, R.; Neven, P.; Paridaens, R.; van den Bogaert, W.; Braun, S.; Janni, W.; Martin, P.; Romain, S.; Hakes, T.; Hudis, C. A.; Norton, L.; Wittes, R.; Giokas, G.; Kondylis, D.; Lissaios, B.; de la Huerta, R.; Sainz, M. G.; Altemus, R.; Camphausen, K.; Cowan, K.; Danforth, D.; Lichter, A.; Lippman, M.; O'Shaughnessy, J.; PierceF, L. J.; Steinberg, S.; Venzon, D.; Zujewski, J. A.; D'Amico, C.; Lioce, M.; Paradiso, A.; Chapman, J. W.; Goss, P. E.; Levine, M. N.; Myles, J. D.; Pater, J. L.; Pritchard, K. I.; Shepherd, L. E.; Tu, D.; Whelan, D.; Zee, B.; Anderson, S.; Bass, G.; Brown, A.; Bryant, J.; Costantino, J.; Fisher, B.; Geyer, C.; Paik, S.; Redmond, C.; Wickerham, L.; Wolmark, N.; Jackson, I. M.; Palmer, M. K.; Perez, E.; Ingle, J. N.; Suman, V. J.; Bengtsson, N. O.; Emdin, S.; Granstrand, B.; Jonsson, H.; Lythgoe, J. P.; Kissin, M.; Erikstein, B.; Hannisdal, E.; Jacobsen, A. B.; Varhaug, J. E.; Gundersen, S.; Hauer-Jensen, M.; Høst, H.; Nissen-Meyer, R.; Mitchell, A. K.; Robertson, J. F. R.; Di Palma, M.; Mathé, G.; Misset, J. L.; Clark, R. M.; LevineF, M.; Whelan, T.; Morimoto, K.; Takatsuka, Y.; Crossley, E.; Harris, A.; Talbot, D.; Taylor, M.; Martin, A. L.; Roché, H.; di Blasio, B.; Ivanov, V.; Semiglazov, V.; Brockschmidt, J.; Cooper, M. R.; Ueo, H.; Falkson, C. I.; Ashley, S.; Makris, A.; Powles, T. J.; Smith, I. E.; Gazet, J. C.; Browne, L.; Graham, P.; Corcoran, N.; Deshpande, N.; di Martino, L.; Douglas, P.; Lindtner, A.; Notter, G.; Bryant, A. J. S.; Ewing, G. H.; Firth, L. A.; Krushen-Kosloski, J. L.; Foster, L.; George, W. D.; Stewart, H. J.; Stroner, P.; Anderson, H.; Malmström, P.; Möller, T. R.; Ringberg, A.; Rydén, L.; Tengrup, I.; Tennvall-Nittby, L.; Arnesson, L.-G.; Carstensen, J.; Dufmats, M.; Nordenskjöld, B.; Söderberg, M.; Carpenter, J. T.; AlbainF, K.; Barlow, W.; CrowleyF, J.; Gralow, J.; Green, S.; Hortobagyi, G.; Livingston, R.; Martino, S.; Osborne, C. K.; Ravdin, P. M.; Murray, N.; Royle, G. T.; Simmonds, P. D.; Askergren, J.; Bäckdahl, M.; Bergh, J.; Fernstad, R.; Fornander, T.; Frisell, J.; Glas, U.; Hatschek, T.; Ideström, K.; Johansson, U.; Perbeck, L.; Rotstein, S.; Rutqvist, L. E.; Sandelin, K.; Singnomklao, T.; Skoog, L.; Somell, A.; Wallgren, A.; Wilking, N.; Maibach, R.; Thürlimann, B.; Holli, K.; Rouhento, K.; Brenner, H.; Hercbergs, A.; Yoshimoto, M.; DeBoer, G.; Paterson, A. H. G.; Fyles, A.; Meakin, J. W.; Panzarella, T.; Shan, Y.; Shao, Y. F.; Wang, X.; Zhao, D. B.; Bahi, J.; Reid, M.; Spittle, M.; Bishop, H.; Bundred, N. J.; Forsyth, S.; Pai, V. R.; Pinder, S. E.; Sestak, I.; Deutsch, G. P.; KwongF, D. L. W.; Senanayake, F.; Bianco, A. R.; Carlomagno, C.; de Laurentiis, M.; de Placido, S.; Broglio, K.; Buzdar, A. U.; Love, R. R.; Garmo, H.; Holmberg, L.; Liljegren, G.; NilssonF, J.; Jones, S. E.; Loesch, D. M.; Janauer, M.; Zielinski, C. C.; Gluz, O.; Nitz, U.; Dunn, J. A.; Hills, R. K.; Lee, M.; Morrison, J. M.; Poole, C.; Litton, A.; Karlsson, P.; Chlebowski, R. T.; Caffier, H.

    2010-01-01

    Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy

  11. Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma

    NARCIS (Netherlands)

    Tummers, W.S. (Willemieke S.); A. Fariña-Sarasqueta (Arantza); M.C. Boonstra (M.); Prevoo, H.A. (Hendrica A.); C.F.M. Sier (Cornelis); J.S.D. Mieog (Sven); H. Morreau (Hans); C.H.J. van Eijck (Casper); P.J.K. Kuppen (P. J K); C.J.H. van de Velde (Cornelis); B.A. Bonsing (Bert); A.L. Vahrmeijer (Alexander L.); Swijnenburg, R.-J. (Rutger-Jan)

    2017-01-01

    textabstractDiscrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this

  12. Analysis of expression of membrane-bound tumor markers in ductal carcinoma in situ of the breast: paving the way for molecular imaging.

    Science.gov (United States)

    Vermeulen, Jeroen F; van der Wall, Elsken; Witkamp, Arjen J; van Diest, Paul J

    2013-07-01

    Achieving radicality during breast conserving surgery for pure ductal carcinoma in situ (DCIS) of the breast and invasive cancer surrounded by DCIS is challenging. Molecular imaging holds promise here, when applied as a tool for image-guided surgery of DCIS. Tissue microarrays containing 24 pure DCIS and 63 DCIS with adjacent invasive breast cancer cases were stained by immunohistochemistry for a panel of membrane-bound targets. GLUT1 expression was present in 60.9%, IGF1-R in 55.2% HER2 in 28.7%, MET in 18.4%, EGFR in 16.1%, CD44v6 in 69%, carbonic anhydrase XII (CAXII) in 24.1% and Mammaglobin in 14.9% of DCIS cases. No expression differences between pure DCIS and DCIS with adjacent cancer were observed. Further, HER2 and EGFR expression were correlated with high grade DCIS (p=0.001) and CAXII with low grade DCIS (p=0.027). A putative panel containing HER2, EGFR, GLUT1 and IGF1-R had a detection rate of 90.2% for DCIS and 78.3% for adjacent breast cancer. We found that membrane-bound targets are more frequently expressed in DCIS than in invasive breast cancer, but that single membrane proteins are too infrequently expressed to serve as single imaging targets for the detection of DCIS. However, a panel of markers consisting of IGF1-R, CD44v6, GLUT1, EGFR, and HER2 was found to be positive in 96.3% of DICS based on marker expression in the adjacent invasive breast cancer as described earlier. This implies that detection of DCIS based on marker expression in the adjacent invasive breast cancer during breast conserving surgery should be possible with a panel of molecular imaging tracers targeting CD44v6, GLUT1, HER2, IGF1-R, and EGFR.

  13. 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.)

  14. 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...

  15. Invasive forest species

    Science.gov (United States)

    Barbara L. Illman

    2006-01-01

    Nonnative organisms that cause a major change to native ecosystems-once called foreign species, biological invasions, alien invasives, exotics, or biohazards–are now generally referred to as invasive species or invasives. invasive species of insects, fungi, plants, fish, and other organisms present a rising threat to natural forest ecosystems worldwide. Invasive...

  16. Predicting invasion in mammographically detected microcalcifcation: a preliminary report

    Directory of Open Access Journals (Sweden)

    Okugawa Homa

    2004-04-01

    Full Text Available Abstract Background With the increased use of mammography for breast cancer screening, the diagnosis of ductal carcinoma in situ (DCIS too has increased. This study was carried out to identify clinical and radiological factors that may predict the presence of invasive disease within mammographically detected microcalcifcation. Materials and methods A retrospective analysis of 13 vacuum-assisted breast biopsies (Mammotome® of mammographic calcification, which were reported to be either DCIS or invasive disease on final histopathology, was carried out. Final surgical pathology was correlated with pre-operative features (clinical, radiological and core histology to predict the presence of an invasive component. Results The overall sensitivity of Mammotome® was 81.8%, while for invasion it was 50%. Small size, granular morphology, increased number and area of calcification cluster may help in predicting invasion on mammography. Conclusions Mammotome® biopsy fails to detect invasion correctly in half the cases despite ascertaining correctness of biopsy with post biopsy x-ray.

  17. Quantifying the extent of invasive carcinoma and margin status in partial mastectomy cases having a gross lesion: is a defined tissue processing protocol needed?

    Science.gov (United States)

    Sneed, George M; Duncan, Lisa D

    2011-11-01

    Accurate estimation of disease extent and margin status is critical when evaluating partial mastectomy cases because both are predictors of recurrence. No published standards exist for processing specimens involved by invasive carcinoma, presumably because such cases have a gross lesion. We retrospectively studied 100 partial mastectomy cases and concluded that a standardized tissue mapping protocol is needed to ensure adequate pathologic examination even when a gross lesion is present. When mapped and unmapped findings were compared, 17 cases (10 with ductal and 7 with lobular carcinoma) had an increase in carcinoma size, 12 cases (9 with ductal and 3 with lobular carcinoma) had an increase in pathologic T stage, and positive margins were found in 8 cases (7 with ductal and 1 with lobular carcinoma). We describe our tissue-mapping protocol, and advocate its use as a standardized protocol for processing all partial mastectomy specimens.

  18. Ductal Carcinoma In Situ: Recent Advances and Future Prospects

    Directory of Open Access Journals (Sweden)

    Kelly Lambert

    2012-01-01

    Full Text Available Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB, adjuvant radiotherapy (RT and endocrine treatment. Methods. Literature review facilitated by Medline, PubMed, Embase and Cochrane databases. Results. DCIS should be managed in the context of a multidisciplinary team. Local control depends upon clear surgical margins (at least 2 mm is generally acceptable. SLNB is not routine, but can be considered in patients undergoing mastectomy (Mx with risk factors for occult invasion. RT following BCS significantly reduces local recurrence (LR, particularly in those at high-risk. There remains a lack of level-1 evidence supporting omission of adjuvant RT in selected low-risk cases. Large, multi-centric or recurrent lesions should be treated by Mx and immediate reconstruction should be discussed. Adjuvant hormonal treatment may reduce the risk of LR in selected cases with hormone sensitive disease. Conclusion. Further research is required to determine the role of new RT regimes and endocrine therapies. Biological profiling and molecular analysis represent an opportunity to improve our understanding of tumour biology in DCIS to rationalise treatment. Reliable identification of low-risk lesions could allow treatment to be less radical.

  19. Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Kohler, Ilona; Bronsert, Peter; Timme, Sylvia; Werner, Martin; Brabletz, Thomas; Hopt, Ulrich Theodor; Schilling, Oliver; Bausch, Dirk; Keck, Tobias; Wellner, Ulrich Friedrich

    2015-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis. Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis. Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  20. Examining the pathogenesis of breast cancer using a novel agent-based model of mammary ductal epithelium dynamics.

    Directory of Open Access Journals (Sweden)

    Joaquin Chapa

    Full Text Available The study of the pathogenesis of breast cancer is challenged by the long time-course of the disease process and the multi-factorial nature of generating oncogenic insults. The characterization of the longitudinal pathogenesis of malignant transformation from baseline normal breast duct epithelial dynamics may provide vital insight into the cascading systems failure that leads to breast cancer. To this end, extensive information on the baseline behavior of normal mammary epithelium and breast cancer oncogenesis was integrated into a computational model termed the Ductal Epithelium Agent-Based Model (DEABM. The DEABM is composed of computational agents that behave according to rules established from published cellular and molecular mechanisms concerning breast duct epithelial dynamics and oncogenesis. The DEABM implements DNA damage and repair, cell division, genetic inheritance and simulates the local tissue environment with hormone excretion and receptor signaling. Unrepaired DNA damage impacts the integrity of the genome within individual cells, including a set of eight representative oncogenes and tumor suppressors previously implicated in breast cancer, with subsequent consequences on successive generations of cells. The DEABM reproduced cellular population dynamics seen during the menstrual cycle and pregnancy, and demonstrated the oncogenic effect of known genetic factors associated with breast cancer, namely TP53 and Myc, in simulations spanning ∼40 years of simulated time. Simulations comparing normal to BRCA1-mutant breast tissue demonstrated rates of invasive cancer development similar to published epidemiologic data with respect to both cumulative incidence over time and estrogen-receptor status. Investigation of the modeling of ERα-positive (ER+ tumorigenesis led to a novel hypothesis implicating the transcription factor and tumor suppressor RUNX3. These data suggest that the DEABM can serve as a potentially valuable framework to

  1. Association Between Hospital Financial Distress and Immediate Breast Reconstruction Surgery After Mastectomy Among Women With Ductal Carcinoma In Situ.

    Science.gov (United States)

    Richards, Catherine A; Rundle, Andrew G; Wright, Jason D; Hershman, Dawn L

    2017-12-06

    Hospital financial distress (HFD) is a state in which a hospital is at risk of closure because of its financial condition. Hospital financial distress may reduce the services a hospital can offer, particularly unprofitable ones. Few studies have assessed the association of HFD with quality of care. To examine the association between HFD and receipt of immediate breast reconstruction surgery after mastectomy among women diagnosed with ductal carcinoma in situ (DCIS). This retrospective cohort study assessed data from the Nationwide Inpatient Sample of 5760 women older than 18 years (mean [SD] age: 57.5 [13.2]) with DCIS who underwent mastectomy in 2008-2012 at hospitals categorized by financial distress. Women treated at 1156 hospitals located in 538 different counties across Arkansas, Arizona, California, Colorado, Connecticut, Florida, Iowa, Kentucky, Massachusetts, Maryland, Missouri, North Carolina, New Hampshire, New Jersey, Nevada, New York, Oregon, Pennsylvania, Rhode Island, Utah, Virginia, Vermont, Washington, Wisconsin, West Virginia, and Wyoming were included. Of these, 2385 women (41.4%) underwent immediate breast reconstruction surgery. Women with invasive cancer were excluded. The database included unique hospital identification variables, and participants were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Data were analyzed from January 1, 2012, to February 28, 2014. The primary outcome was the adjusted association between HFD and receipt of immediate breast reconstruction surgery after mastectomy. In this analysis of database information, 2385 of 5760 women (41.4%) received immediate breast reconstruction surgery. Of these, 693 (36.7%) were treated at a hospital under high HFD and received immediate breast reconstruction surgery compared with 863 (44.0%) treated at a hospital under low HFD (P financial strength of the hospital where a patient receives treatment is associated with receipt of

  2. Variable Appearances of Ductal Carcinoma In Situ Calcifications on Digital Mammography, Synthesized Mammography, and Tomosynthesis: A Pictorial Essay.

    Science.gov (United States)

    Hwang, Esther; Szabo, Janet; Sonnenblick, Emily B; Margolies, Laurie R

    2017-09-22

    This pictorial essay demonstrates the variable appearances of ductal carcinoma in situ on full-field digital mammography, synthesized mammography, and digital breast tomosynthesis. The spectrum of intercase and intracase variability suggests further refinement of reconstruction algorithms for synthesized mammography may be necessary to maximize early detection of ductal carcinoma in situ. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  3. Sarcomatoid Carcinoma of the Prostate: Ductal Adenocarcinoma and Stromal Sarcoma-Like Appearance: A Rare Association

    Directory of Open Access Journals (Sweden)

    David Parada

    2011-01-01

    Full Text Available Sarcomatoid carcinoma (SC of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.

  4. A case report: Blastic plasmacytoid dendritic cell neoplasm is misdiagnosed as breast infiltrating ductal carcinoma.

    Science.gov (United States)

    Chen, Ko-Chin; Su, Tzu-Cheng; Chen, Dar-Ren; Liou, Jia-Hung

    2015-02-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic tumor that typically occurs in older adults. Patients with BPDCN usually present with solitary or multiple skin lesions. Localized or disseminated lymphadenopathy at presentation is common. A case report illustrating histopathologically proven BPDCN initially misdiagnosed as breast infiltrating ductal carcinoma in a 39-year-old woman is presented. In this case, the patient presented with a breast mass without an obvious skin lesion initially. The morphology of the tumor cells mimicked high grade breast carcinoma cells. Without complete immunohistochemical study, this case was initially misdiagnosed as infiltrating ductal carcinoma. Reviewing the previous literature about BPDCN, no case with a breast mass and an absence of characteristic skin lesions initially has been reported. The purpose for which we are discussing this case is to reduce misdiagnosis when the initial symptom is unusual. © The Author(s) 2014.

  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

    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. In the pr......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...... underwent SLNB. The use of SLNB increased from 26.6% in 2004 to 65.1% in 2015. A total of 1877 (71.7%) patients underwent breast-conserving surgery (BCS), and 577 (22.0%) underwent mastectomy, of which 43.9% and 86.0% respectively had a concomitant SLNB. The SLNB was performed in 23.8% of 454 patients...

  6. 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.

  7. Total pancreatectomy for pancreatic ductal adenocarcinoma: review of the National Cancer Data Base.

    Science.gov (United States)

    Johnston, W Cory; Hoen, Helena M; Cassera, Maria A; Newell, Pippa H; Hammill, Chet W; Hansen, Paul D; Wolf, Ronald F

    2016-01-01

    Total pancreatectomy is infrequently performed for pancreatic cancer. Perceived operative mortality and questionable survival benefit deter many surgeons. Clinical outcomes, described in single-center series, remain largely unknown. The National Cancer Database was queried for cases of pancreatic ductal adenocarcinoma undergoing total pancreatectomy (1998-2011). Univariate survival analyses were performed for 21 variables: demographic (8), tumor characteristics (5), surgery outcomes (6), and adjuvant therapy (2). The Log-rank test of differences in Kaplan-Meier survival curves was used for categorical variables. Variables with p total pancreatectomy is a reasonable option for selected patients with pancreatic ductal adenocarcinoma, survival of the entire group is limited. Operative mortality is improved from prior reports. Greater survival benefits were seen in younger patients with smaller, node negative tumors resected with negative margins in academic research centers. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  8. Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

    Science.gov (United States)

    Suhane, Sonal; Berel, Dror; Ramanujan, V Krishnan

    2011-09-09

    We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. 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

    2015-01-01

    Aims 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. Methods and results 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. Conclusions 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. PMID:25283075

  10. Investigating Ductal Carcinoma in Situ Using Noninvasive Imaging of Genetically Engineered Mouse Models

    Science.gov (United States)

    2013-08-01

    detection of breast cancer have yielded a major reduction in mortality because of the downward stage shifting of cancers at initial diagnosis : more women...Endometrial cancer 5.44E-03 Arrhythmogenic right ventricular cardiomyopathy 5.47E-03 VEGF signaling pathway 6.22E-03 Phosphatidylinosftol signaling...Conference statement: Diagnosis and Management of Ductal Carcinoma In Situ September 22-24, 2009 Journal of the National Cancer Institute 102 161-9

  11. Incidental detection of filarial worm in metastatic axillary lymph node from ductal carcinoma breast

    Directory of Open Access Journals (Sweden)

    Ranjan Agrawal

    2015-01-01

    Full Text Available Filariasis is a major disease of the tropics. Frequently, lymphatics of the lower limbs, retroperitoneal tissues, spermatic cord, epididymis, and mammary glands are involved. Simultaneous filariasis along with another underlying disease is rare. We present a rare case of filariasis of the axillary lymph node in a modified radical mastectomy specimen, which also showed metastatic deposits of ductal carcinoma breast. The case is presented due to its rarity.

  12. Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia.

    Science.gov (United States)

    Shi, G; DiRenzo, D; Qu, C; Barney, D; Miley, D; Konieczny, S F

    2013-04-11

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers owing to a number of characteristics including difficulty in establishing early diagnosis and the absence of effective therapeutic regimens. A large number of genetic alterations have been ascribed to PDAC with mutations in the KRAS2 proto-oncogene thought to be an early event in the progression of disease. Recent lineage-tracing studies have shown that acinar cells expressing mutant Kras(G12D) are induced to transdifferentiate, generating duct-like cells through a process known as acinar-ductal metaplasia (ADM). ADM lesions then convert to precancerous pancreatic intraepithelial neoplasia (PanIN) that progresses to PDAC over time. Thus, understanding the earliest events involved in ADM/PanIN formation would provide much needed information on the molecular pathways that are instrumental in initiating this disease. As studying the transition of acinar cells to metaplastic ductal cells in vivo is complicated by analysis of the entire organ, an in vitro three dimensional (3D) culture system was used to model ADM outside the animal. Kras(G12D)-expressing acinar cells rapidly underwent ADM in 3D culture, forming ductal cysts that silenced acinar genes and activated duct genes, characteristics associated with in vivo ADM/PanIN lesions. Analysis of downstream KRAS signaling events established a critical importance for the Raf/MEK/ERK pathway in ADM induction. In addition, forced expression of the acinar-restricted transcription factor Mist1, which is critical to acinar cell organization, significantly attenuated Kras(G12D)-induced ADM/PanIN formation. These results suggest that maintaining MIST1 activity in Kras(G12D)-expressing acinar cells can partially mitigate the transformation activity of oncogenic KRAS. Future therapeutics that target both the MAPK pathway and Mist1 transcriptional networks may show promising efficacy in combating this deadly disease.

  13. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    OpenAIRE

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce

    2008-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes...

  14. STAT5 deletion in macrophages alters ductal elongation and branching during mammary gland development.

    Science.gov (United States)

    Brady, Nicholas J; Farrar, Michael A; Schwertfeger, Kathryn L

    2017-08-01

    Macrophages are required for proper mammary gland development and maintaining tissue homeostasis. However, the mechanisms by which macrophages regulate this process remain unclear. Here, we identify STAT5 as an important regulator of macrophage function in the developing mammary gland. Analysis of mammary glands from mice with STAT5-deficient macrophages demonstrates delayed ductal elongation, enhanced ductal branching and increased epithelial proliferation. Further analysis reveals that STAT5 deletion in macrophages leads to enhanced expression of proliferative factors such as Cyp19a1/aromatase and IL-6. Mechanistic studies demonstrate that STAT5 binds directly to the Cyp19a1 promoter in macrophages to suppress gene expression and that loss of STAT5 results in enhanced stromal expression of aromatase. Finally, we demonstrate that STAT5 deletion in macrophages cooperates with oncogenic initiation in mammary epithelium to accelerate the formation of estrogen receptor (ER)-positive hyperplasias. These studies establish the importance of STAT5 in macrophages during ductal morphogenesis in the mammary gland and demonstrate that altering STAT5 function in macrophages can affect the development of tissue-specific disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Nuclear Position and Shape Deformation of Chromosome 8 Territories in Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sylvia Timme

    2011-01-01

    Full Text Available Cell type specific radial positioning of chromosome territories (CTs and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8 in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH with whole chromosome painting (WCP probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma.

  16. Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas.

    Science.gov (United States)

    Shonaka, Tatsuya; Inagaki, Mitsuhiro; Akabane, Hiromitsu; Yanagida, Naoyuki; Shomura, Hiroki; Yanagawa, Nobuyuki; Oikawa, Kensuke; Nakano, Shiro

    2014-09-07

    In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct. Mucin5AC, α1-antitrypsin (α-AT) and carcinoembryonic antigen (CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

  17. Yes-associated protein mediates immune reprogramming in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Murakami, S; Shahbazian, D; Surana, R; Zhang, W; Chen, H; Graham, G T; White, S M; Weiner, L M; Yi, C

    2017-03-02

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high degree of inflammation and profound immune suppression. Here we identify Yes-associated protein (Yap) as a critical regulator of the immunosuppressive microenvironment in both mouse and human PDAC. Within Kras:p53 mutant pancreatic ductal cells, Yap drives the expression and secretion of multiple cytokines/chemokines, which in turn promote the differentiation and accumulation of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Pancreas-specific knockout of Yap or antibody-mediated depletion of MDSCs promoted macrophage reprogramming, reactivation of T cells, apoptosis of Kras mutant neoplastic ductal cells and pancreatic regeneration after acute pancreatitis. In primary human PDAC, YAP expression levels strongly correlate with an MDSC gene signature, and high expression of YAP or MDSC-related genes predicts decreased survival in PDAC patients. These results reveal multifaceted roles of YAP in PDAC pathogenesis and underscore its promise as a therapeutic target for this deadly disease.

  18. Synchronous Malignant Phyllodes Tumor with Skin Ulceration and Invasive Carcinoma as Collision Tumor.

    Science.gov (United States)

    Muthusamy, Rajeshwari K; Mehta, Sangita S

    2017-01-01

    Phyllodes tumor is a rare fibroepithelial biphasic tumor of the breast composed of hypercellular mesenchymal stroma and double-layered epithelial component, arranged in clefts with leaf-like projections. Phyllodes tumor with coincidental presence of invasive carcinoma or in situ ductal carcinoma in the same or distinct breast is a rare occurrence, documented by some reports. Invasive carcinoma can be seen within or outside the phyllodes tumor. Skin ulceration by malignant phyllodes tumor with coexisting invasive carcinoma as collision tumor is extremely rare. Here, we report an extremely rare presentation of malignant phyllodes tumor as a giant fungating mass with distinct invasive carcinoma in the same breast in a 51-year-old female.

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

    Science.gov (United States)

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

    2012-08-06

    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.

  20. 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

  1. 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...... by necrosis. Moreover, the P2X7R-pore antagonist, A438079, prevented ATP-induced pore formation and cell death. Second, in basal conditions and with low concentrations of ATP/BzATP, the P2X7R allosteric inhibitor AZ10606120 reduced proliferation in all PDAC cell lines. P2X7R also affected other key...

  2. 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...... of patients diagnosed with DCIS, making a precise localization of nonpalpable DCIS lesions even more important....

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Is the upgrade rate of atypical ductal hyperplasia diagnosed by core needle biopsy of calcifications different for digital and film-screen mammography?

    Science.gov (United States)

    McLaughlin, Carol T; Neal, Colleen H; Helvie, Mark A

    2014-10-01

    The purpose of this study was to establish the upgrade rate of atypical ductal hyperplasia (ADH) diagnosed by stereotactic vacuum-assisted core needle biopsy for calcifications detected by digital mammography as compared with film-screen mammography. A retrospective record search identified 101 cases of ADH. Criteria included women with calcifications biopsied using stereotactic vacuum-assisted core needle biopsy at our institution between January 2001 and December 2011. The center transitioned from film-screen mammography in 2001 to all digital mammography by 2010. Stereotactic vacuum-assisted core needle biopsies were performed using 11-gauge (59/101 [58%]) or 8-gauge (42/101 [42%]) needles. All pathology was interpreted by breast pathologists using standard criteria. Of 101 cases of ADH, 57 (56.4%) were detected using digital and 44 (43.6%) were detected using film-screen mammography. Seven of 57 (12.3%) cases of ADH detected by digital mammography were upgraded to ductal carcinoma in situ (DCIS) (n = 6) or invasive cancer (n = 1). Six of 44 (13.6%) cases of ADH detected by film-screen mammography were upgraded to DCIS (n = 5) or invasive cancer (n = 1) (p = 0.84). There was a trend toward low-grade DCIS in cases detected by digital mammography (3/7 [42.9%]) as compared with film-screen mammography (1/6 [16.7%]) (p = 0.68). A nonsignificant overall higher percentage of upgrades occurred when calcifications were not completely removed (10/52 [19.2%]) as compared with completely removed (3/47 [6.4%]). There was no difference in upgrade rate of stereotactic vacuum-assisted core needle biopsy performed using 11-gauge (7/59 [11.9%]) versus 8-gauge (6/42 [14.3%]) needles. The upgrade rate of ADH diagnosed by stereotactic vacuum-assisted core needle biopsy was not significantly different between digital and film-screen mammography. The current recommendation for excision of ADH diagnosed by stereotactic vacuum-assisted core needle biopsy should be applied to ADH

  8. A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination

    Science.gov (United States)

    Frittoli, Emanuela; Palamidessi, Andrea; Marighetti, Paola; Confalonieri, Stefano; Bianchi, Fabrizio; Malinverno, Chiara; Mazzarol, Giovanni; Viale, Giuseppe; Martin-Padura, Ines; Garré, Massimilliano; Parazzoli, Dario; Mattei, Valentina; Cortellino, Salvatore; Bertalot, Giovanni

    2014-01-01

    The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5–dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and β3 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program. PMID:25049275

  9. Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma.

    Science.gov (United States)

    Shah, Chirag; Wilkinson, J Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina; Vicini, Frank

    2011-11-15

    We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p invasive lobular versus invasive ductal histology. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Invasive lobular carcinoma of the breast with extracellular mucin: A case report.

    Science.gov (United States)

    Gómez Macías, G S; Pérez Saucedo, J E; Cardona Huerta, S; Garza Montemayor, M; Villarreal Garza, C; García Hernández, I

    2016-01-01

    Invasive lobular carcinoma is the second most common histological type of breast carcinoma, accounting for approximately 5%-15% of all invasive breast cancers. The extracellular mucin secretion is by default a feature of ductal carcinoma. Only four cases of infiltrative lobular carcinoma with extracellular mucin have been report. A 60 year old female asymptomatic patient with palpable breast mass and architectural distortion by mammography on external upper quadrant of the right breast was diagnosed as invasive lobular carcinoma with extracellular mucin in the resection, confirmed with immunohistochemistry markers. Previous report in the literature of four cases of Invasive lobular carcinoma of breast with extracellular mucin, all of them sharing the same histologic features: the presence of extracellular and intracellular mucin with appearance of infiltrates lobular carcinoma with signet ring cells and "Indian files". It is important to know that extracellular mucin production is not exclusive of ductal lesions and keep in mind the lobular carcinomas with extracellular mucin as a differential diagnosis. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Predicting invasive breast cancer versus DCIS in different age groups.

    Science.gov (United States)

    Ayvaci, Mehmet U S; Alagoz, Oguzhan; Chhatwal, Jagpreet; Munoz del Rio, Alejandro; Sickles, Edward A; Nassif, Houssam; Kerlikowske, Karla; Burnside, Elizabeth S

    2014-08-11

    Increasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age. We analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women ≥ 65 (older group), women 50-64 (middle age group), and women group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC). The models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer. Clinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age.

  12. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853. EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.

    Science.gov (United States)

    Julien, J P; Bijker, N; Fentiman, I S; Peterse, J L; Delledonne, V; Rouanet, P; Avril, A; Sylvester, R; Mignolet, F; Bartelink, H; Van Dongen, J A

    2000-02-12

    Ductal carcinoma in situ (DCIS) of the breast is a disorder that has become more common since it may manifest as microcalcifications that can be detected by screening mammography. Since selected women with invasive cancer can be treated safely with breast conservation therapy it is paradoxical that total mastectomy has remained the standard treatment for DCIS. We did a randomised phase III clinical trial to investigate the role of radiotherapy after complete local excision of DCIS. Between 1986 and 1996, women with clinically or mammographically detected DCIS measuring less than or equal to 5 cm were treated by complete local excision of the lesion and then randomly assigned to either no further treatment (n=503) or to radiotherapy (n=507; 50 Gy in 5 weeks to the whole breast). The median duration of follow-up was 4.25 years (maximum 12.0 years). All analyses were by intention to treat. 500 patients were followed up in the no further treatment group and 502 in the radiotherapy group. In the no further treatment group 83 women had local recurrence (44 recurrences of DCIS, and 40 invasive breast cancer). In the radiotherapy group 53 women had local recurrences (29 recurrences of DCIS, and 24 invasive breast cancer). The 4-year local relapse-free was 84% in the group treated with local excision alone compared with 91% in the women treated by local excision plus radiotherapy (log rank p=0.005; hazard ratio 0.62). Similar reductions in the risk of invasive (40%, p=0.04) and non-invasive (35%, p=0.06) local recurrence were seen. Radiotherapy after local excision for DCIS, as compared with local excision alone, reduced the overall number of both invasive and non-invasive recurrences in the ipsilateral breast at a median follow-up of 4.25 years.

  13. Oleic acid and glucose regulate glucagon-like peptide 1 receptor expression in a rat pancreatic ductal cell line

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. Gastrin induces ductal cell dedifferentiation and β-cell neogenesis after 90% pancreatectomy.

    Science.gov (United States)

    Téllez, Noèlia; Montanya, Eduard

    2014-10-01

    Induction of β-cell mass regeneration is a potentially curative treatment for diabetes. We have recently found that long-term gastrin treatment results in improved metabolic control and β-cell mass expansion in 95% pancreatectomised (Px) rats. In this study, we investigated the underlying mechanisms of gastrin-induced β-cell mass expansion after Px. After 90%-Px, rats were treated with gastrin (Px+G) or vehicle (Px+V), pancreatic remnants were harvested on days 1, 3, 5, 7, and 14 and used for gene expression, protein immunolocalisation and morphometric analyses. Gastrin- and vehicle-treated Px rats showed similar blood glucose levels throughout the study. Initially, after Px, focal areas of regeneration, showing mesenchymal cells surrounding ductal structures that expressed the cholecystokinin B receptor, were identified. These focal areas of regeneration were similar in size and cell composition in the Px+G and Px+V groups. However, in the Px+G group, the ductal structures showed lower levels of keratin 20 and β-catenin (indicative of duct dedifferentiation) and higher levels of expression of neurogenin 3 and NKX6-1 (indicative of endocrine progenitor phenotype), as compared with Px+V rats. In Px+G rats, β-cell mass and the number of scattered β-cells were significantly increased compared with Px+V rats, whereas β-cell replication and apoptosis were similar in the two groups. These results indicate that gastrin treatment-enhanced dedifferentiation and reprogramming of regenerative ductal cells in Px rats, increased β-cell neogenesis and fostered β-cell mass expansion. © 2014 Society for Endocrinology.

  15. 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

  16. Overview of Pre-Clinical and Clinical Studies Targeting Angiogenesis in Pancreatic Ductal Adenocarcinoma

    Science.gov (United States)

    Craven, Kelly E.; Gore, Jesse; Korc, Murray

    2016-01-01

    The importance of angiogenesis in Pancreatic Ductal Adenocarcinoma (PDAC) and its therapeutic potential have been explored in both pre-clinical and clinical studies. Human PDACs overexpress a number of angiogenic factors and their cognate high-affinity receptors, and anti-angiogenic agents reduce tumor volume, metastasis, and microvessel density (MVD), and improve survival in subcutaneous and orthotopic pre-clinical models. Nonetheless, clinical trials using anti-angiogenic therapy have been overwhelmingly unsuccessful. This review will focus on these pre-clinical and clinical studies, the potential reasons for failure in the clinical setting, and ways these shortcomings could be addressed in future investigations of angiogenic mechanisms in PDAC. PMID:26723874

  17. A benign presentation of primary ductal adenocarcinoma of lacrimal gland: A rare malignancy

    Directory of Open Access Journals (Sweden)

    Lindfay Laura Lau

    2015-01-01

    Full Text Available A 34-year-old patient with a swelling over the upper eyelid for nearly 1 year was seen in our clinic. The history, examination and investigations were suggestive of a benign lacrimal gland tumor. The tumor and lacrimal gland were resected. Subsequent histopathological examination revealed the tumor was a primary ductal adenocarcinoma of the lacrimal gland. This is a very rare tumor with less than half a dozen cases reported so far. This case report is being presented to highlight an unusual presentation of this rare malignancy.

  18. 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 PKD2 functions downstream of BICC1 in preventing cyst formation in the pancreas. Moreover, the analysis highlights immune cell infiltration and stromal reaction developing early in the pancreas of Bicc1 knockout mice. In addition to these functions in duct morphogenesis, BICC1 regulates NEUROG3......(+) 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...

  19. FEATURES OF ISLET-LIKE CLUSTERS GENERATION IN PANCREATIC DUCTAL CELL MOLOLAYER CULTURING

    Directory of Open Access Journals (Sweden)

    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. 

  20. 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

    signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9......, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation...

  1. Intercalated duct cell is starting point in development of pancreatic ductal carcinoma?

    Directory of Open Access Journals (Sweden)

    Yamaguchi Toshikazu

    2005-01-01

    Full Text Available Abstract Background Although it is well known that the pancreatic ductal carcinoma may develop having a relationship to the mucous gland hyperplasia (MGH with atypia (PanIN-1B by PanIN system, the starting point of this atypical MGH is unclear. To know it, we examined the pancreas tissue using many methods described below. Methods 1. Twenty-seven surgically resected pancreas tissue specimens, including pancreatic ductal carcinomas (PDC, chronic pancreatitis and normal pancreas, were investigated using immunohistochemical stainings for MUC1, MUC6, 45M1, Ki67 and p53. 2. DNA extraction and analysis of K-ras mutation at codon 12 using microdissection method: The paraffin blocks with 16 regions including the intercalated duct cell (IC adjacant to the atypical MGH were prepared for DNA extraction. Mutation of K-ras codon 12 was analized and compared in enriched polymerase chain reaction-enzyme-linked minisequence assay (PCR-ELMA. Results 1. In the normal pancreas, although no positive cell was seen in 45M1, p53, Ki67, the cytoplasm of IC were always positive for MUC1 and sometimes positive for MUC6. In the pancreas with fibrosis or inflammation, MGH was positive for MUC6 and 45M1. And atypical MGH was positive for MUC1, MUC6 and 45M1. Some IC adjacent to the atypical MGH was positive for Ki67 as well as atypical MGH. The carcinoma cells in all cases of PDC were diffusely positive for MUC1, 45M1, p53 and Ki67, and focally positive for MUC6. 2. In K-ras mutation, we examined the regions including IC adjacent to the atypical MGH, because the immunohistochemical apomucin stainings of these regions resembled those of PDC as decribed above. And K-ras mutation was confirmed in 12 of 16 regions (75%. All mutations were a single mutation, in 6 regions GTT was detected, in 4 regions GAT was detected and in 2 region AGT was detected. Conclusion Some intercalated duct cell may be the starting point of the pancreatic ductal carcinoma, because the exhibitions of

  2. Ductal Carcinoma In Situ Arising in a Benign Phyllodes Tumor: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Dong Jae; Kim, Dae Bong; Roh, Ji Hyeon; Kwak, Beom Seok [Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang (Korea, Republic of)

    2013-03-15

    A 42-year-old woman was presented with an ovoid mass detected on a mammography. Her physical examination revealed a 2 cm ill-defined mass in the right upper outer breast. A sonogram demonstrated a 1.9 cm ovoid, partially microlobulated and partially well-circumscribed, and an isoechoic mass with increased vascularity on Doppler imaging. Surgical excision was performed and the pathology revealed ductal carcinoma in situ (DCIS) in a phyllodes tumor. DCIS within a phyllodes tumor is a very rare event. Here, we report on a case of DCIS in a phyllodes tumor.

  3. 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.

  4. 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

    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...... 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......) gene families, Vav1, monoglyceride lipase and NADP+-dependent malic enzyme, exhibited altered expression in MCB vs. ductal breast cancer, and the differences for some of these genes were confirmed on an extended panel of cell lines by quantitative PCR. Immunohistochemical analysis further established...

  5. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

    Directory of Open Access Journals (Sweden)

    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.

  6. A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud.

    Science.gov (United States)

    Paine, Ingrid; Chauviere, Arnaud; Landua, John; Sreekumar, Amulya; Cristini, Vittorio; Rosen, Jeffrey; Lewis, Michael T

    2016-04-01

    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.

  7. Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents.

    Science.gov (United States)

    Grippo, Paul J; Sandgren, Eric P

    2012-09-01

    Several important characteristics of exocrine pancreatic tumor pathogenesis remain incompletely defined, including identification of the cell of origin. Most human pancreatic neoplasms are ductal adenocarcinomas. However, acinar cells have been proposed as the source of some ductal neoplasms through a process of acinar-to-ductal metaplasia. The oncogenic transcription factor c-myc is associated with human pancreatic neoplasms. Transgenic mice overexpressing c-myc under control of acinar cell-specific elastase (Ela) gene regulatory elements not only develop acinar cell carcinomas but also mixed neoplasms that display both acinar-like neoplastic cells and duct-like neoplastic cells. In this report, we demonstrate that, first, c-myc is sufficient to induce acinar hyperplasia, though neoplastic lesions develop focally. Second, cell proliferation remains elevated in the neoplastic duct cell compartment of mixed neoplasms. Third, the proliferation/apoptosis ratio in cells from all lesion types remains constant, suggesting that differential regulation of these processes is not a feature of cancer progression in this model. Fourth, before the development of mixed neoplasms, there is transcriptional activation of the duct cell-specific cytokeratin-19 gene promoter in multicellular foci of amylase-positive acinar neoplasms. This observation provides direct evidence for metaplasia as the mechanism underlying development of ductal neoplastic cells within the context of an acinar neoplasm and suggests that the stimulus for this transformation acts over a multicellular domain or field within a neoplasm. Finally, focal ductal elements develop in some acinar cell carcinomas in Ela-c-myc transgenic rats, indicating that myc-associated acinar-to-ductal metaplasia is not restricted to the mouse. Copyright © 2011 UICC.

  8. 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.

  9. 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.

  10. Structural imaging of the pancreas in rat using micro-CT: application to a non-invasivelongitudinal evaluation of pancreatic ductal carcinoma monitoring

    Directory of Open Access Journals (Sweden)

    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.

  11. Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    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.

  12. An increased expression of long non-coding RNA PANDAR promotes cell proliferation and inhibits cell apoptosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Jiang, Yuehong; Feng, Enhang; Sun, Lifang; Jin, Wei; You, Yuhong; Yao, Yue; Xu, Yi

    2017-11-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed. The functional roles of lncRNA PANDAR in PDAC cells were evaluated both in vitro and in vivo. The results indicated that PANDAR was aberrantly overexpressed in PDAC tissues and cell lines, and this overexpression was closely associated with tumor stage and vascular invasion in PDAC patients. Besides, silencing of PANDAR exerted tumor suppressive effect via reducing cell proliferation, colony-forming ability, inducing cell cycle G0/G1 arrest and apoptosis in PANC1 and Capan-2 cells. Further in vivo study confirmed the oncogenesis role of PANDAR in PDAC cells. Overall, our findings may help to develop a potential therapeutic target for the patients with PDAC. Copyright © 2017. Published by Elsevier Masson SAS.

  13. Differentiated expression of estrogen receptors (ER and progesterone receptors (PgR in ductal breast cancers.

    Directory of Open Access Journals (Sweden)

    Piotr Dziegiel

    2009-05-01

    Full Text Available Contents of estrogen receptors (ER and progesterone receptors (PgR in cells of breast cancers represent strong predictive factors. The higher is the contents of ER and PgR in breast cancer, the higher is a probability of obtaining a response to hormonal therapy and prognosis for the patient is better. In a routine manner, all tumours of mammary gland are subjected to evaluation of ER and PgR expression using immunohistochemistry. Forty ductal breast cancers (pT2N0 were subjected to an immunohistochemical evaluation (IHC aimed at detection of ER and PgR expression. From every tumour three samples were taken for immunohistochemical studies: the lateral one from the side of axilla (ER-1; PgR-1; the median one (ER-2; PgR-2 and the medial one from the side of sternum (ER-3; PgR-3. The levels of both ER and PgR expression proved to be highly differentiated between the medial zone of the tumour and its periphery. The distinct expression of ER and PgR in ductal breast cancers, dependent on evaluated zone of the tumour, confirms its heterogeneous character and exerts an effect on the type of applied treatment.

  14. 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.

  15. Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth.

    Science.gov (United States)

    Hammer, Anisha M; Sizemore, Gina M; Shukla, Vasudha C; Avendano, Alex; Sizemore, Steven T; Chang, Jonathan J; Kladney, Raleigh D; Cuitiño, Maria C; Thies, Katie A; Verfurth, Quinn; Chakravarti, Arnab; Yee, Lisa D; Leone, Gustavo; Song, Jonathan W; Ghadiali, Samir N; Ostrowski, Michael C

    2017-06-01

    The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition. Mammary fibroblasts with PDGFRα hyperactivation also decreased hydraulic permeability of a collagen substrate in an in vitro microfluidic device assay, which was mitigated by inhibition of either PDGFRα or HA. Fibrosis seen in this model significantly increased the overall stiffness of the mammary gland as measured by atomic force microscopy. Further, mammary tumor cells injected orthotopically in the fat pads of mice with stromal activation of PDGFRα grew larger tumors compared to controls. Taken together, our data establish that aberrant stromal PDGFRα signaling disrupts ECM homeostasis during mammary gland development, resulting in increased mammary stiffness and increased potential for tumor growth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Stromal PDGFR-α Activation Enhances Matrix Stiffness, Impedes Mammary Ductal Development, and Accelerates Tumor Growth

    Directory of Open Access Journals (Sweden)

    Anisha M. Hammer

    2017-06-01

    Full Text Available The extracellular matrix (ECM is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA and collagen deposition. Mammary fibroblasts with PDGFRα hyperactivation also decreased hydraulic permeability of a collagen substrate in an in vitro microfluidic device assay, which was mitigated by inhibition of either PDGFRα or HA. Fibrosis seen in this model significantly increased the overall stiffness of the mammary gland as measured by atomic force microscopy. Further, mammary tumor cells injected orthotopically in the fat pads of mice with stromal activation of PDGFRα grew larger tumors compared to controls. Taken together, our data establish that aberrant stromal PDGFRα signaling disrupts ECM homeostasis during mammary gland development, resulting in increased mammary stiffness and increased potential for tumor growth.

  17. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches?

    Science.gov (United States)

    Croome, Kristopher P; Farnell, Michael B; Que, Florencia G; Reid-Lombardo, K Marie; Truty, Mark J; Nagorney, David M; Kendrick, Michael L

    2014-10-01

    To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma. Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered. We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013. Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5-73 days) than in the TLPD group (6 days; range, 4-118 days; P advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

  18. Atypical Ductal Hyperplasia (ADH): Can the Sonoelastography Predict the Upgrade of ADH to Malignancy?

    Energy Technology Data Exchange (ETDEWEB)

    An, Yeong Yi; Kim, Sung Hun; Kang, Bong Joo [Dept. of Radiology, Seoul St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Ah Won [Dept. of Pathology, Seoul St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of); Song, Byung Joo [Dept. of Surgery, Seoul St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2011-04-15

    To evaluate whether the sonoelastographic features of atypical ductal hyperplasia (ADH) can be used to predict an upgrade to malignancy. Conventional US and sonoelastographic images were available in 17 women with 18 ADH lesions diagnosed by sonographically guided core needle biopsy. Conventional US findings were analyzed according to the Breast Imaging Reporting and Data System classification. Elastographic images were classified into 5 elasticity scores according to the ITOH classification. In addition, the strain ratio between the mass and surrounding fat tissue as well as the mammographic features were reviewed. All lesions underwent subsequent surgical excision and a correlation was found for sonoelastographic and conventional US findings with pathologic results. Of the 18 ADH lesions that underwent surgical excision, four were found to be malignant (underestimation rate of 22.2%). Moreover, there was no significant difference in elasticity score (p=0.054) and strain ratio (p=0.375) between atypical ductal hyperplasia and lesions upgraded to malignancy on elastography. A mass with microcalcifications on mammography had a significantly higher association with malignancy and microcalcifications, as opposed to the absence of a mass, which was in all cases, benign (p=0.036).

  19. Invasive pleomorphic lobular carcinoma, negative for ER, PR and Her/2neu--a case report.

    Science.gov (United States)

    Manucha, Varsha; Khilko, Natalya; Reilly, Kathleen; Zhang, Xinmin

    2011-01-30

    Pleomorphic variant of lobular carcinoma is a recently described variant of invasive lobular carcinoma. It is reported to be positive for estrogen receptors and progesterone receptors and over express Her2/neu in most cases. We present here a case of invasive variant of pleomorphic lobular carcinoma with coexisting classic and pleomorphic variants of lobular carcinoma in situ along with focal ductal carcinoma in situ. The immunohistochemical results on hormone receptors and high molecular weight cytokeratins in all the above components of the tumor are presented. The invasive tumor was negative for estrogen receptors, progesterone receptors and Her2/neu. Most foci of lobular carcinoma in situ showed morphogenic heterogeneity and a corresponding heterogeneous staining for hormone receptors. The high molecular weight cytokeratins (CK5/6 and CK 903) were non contributory in establishing diagnosis.

  20. The diagnosis and management of pre-invasive breast disease: the role of new diagnostic techniques.

    Science.gov (United States)

    Nerurkar, Ashutosh; Osin, Peter

    2003-01-01

    In recent years we have seen significantly increased use of minimally invasive diagnostic techniques in the management of breast disease. There is wide recognition of fine needle aspiration and core biopsy as the principal diagnostic methods. However, concerns exist regarding their reliability. This article provides a brief overview of the major diagnostic issues related to use of fine needle aspiration, core biopsy and ductal lavage. It summarizes areas of use for each technique, outlines the main diagnostic pitfalls and their causes, and provides a perspective on future developments in the field.

  1. Invasive lobular carcinoma with extracellular mucin production and HER-2 overexpression: a case report and further case studies

    Directory of Open Access Journals (Sweden)

    Bhargava Rohit

    2010-06-01

    Full Text Available Abstract Invasive lobular carcinomas (ILC of breast typically demonstrate intracytoplasmic mucin. We present a unique case of classical type ILC with abundant extracellular mucin and strong ERBB2 (HER2/neu expression confirmed by immunohistochemistry and fluorescent in situ hybridization. Dual E-cadherin/p120 immunohistochemical stain demonstrated complete loss of membranous E-cadherin and the presence of diffuse cytoplasmic p120 staining, confirming the lobular phenotype. The tumor cells showed ductal-like cytoplasmic MUC1 staining, but were negative for MUC2 and other mucin gene markers. In addition, studies of tissue microarrays of 80 breast carcinomas with mucinous differentiation revealed 4 pure mucinous carcinomas showing significantly reduced E-cadherin staining without redistribution of p120 into cytoplasm. The findings suggest that the presence of extracellular mucin does not exclude a diagnosis of lobular carcinoma, and the morphologic and molecular characteristics of lobular and ductal carcinomas are more complex than previously appreciated.

  2. MRI of the breast in patients with DCIS to exclude the presence of invasive disease

    Energy Technology Data Exchange (ETDEWEB)

    Deurloo, Eline E. [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Sriram, Jincey D.; Rutgers, Emiel J.T. [Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Surgery, Amsterdam (Netherlands); Teertstra, Hendrik J.; Loo, Claudette E. [Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Wesseling, Jelle [Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Center Utrecht, Department of Radiology, Image Sciences Institute, Utrecht (Netherlands)

    2012-07-15

    Core biopsy underestimates invasion in more than 20% of patients with preoperatively diagnosed ductal carcinoma in situ (DCIS) without evidence of invasion (pure DCIS). The aim of the current study was to evaluate the efficacy of preoperative magnetic resonance imaging (MRI) to discriminate between patients with DCIS who are at high risk of invasive breast cancer and patients at low risk. One hundred and twenty-five patients, preoperatively diagnosed with pure DCIS (128 lesions; 3 bilateral) by core-needle biopsy, were prospectively included. Clinical, mammographic, histological (core biopsy) and MRI features were assessed. All patients underwent breast surgery. Analyses were performed to identify features associated with presence of invasion. Eighteen lesions (14.1%) showed invasion on final histology. Seventy-three lesions (57%) showed suspicious enhancement on MRI with a type 1 (n = 12, 16.4%), type 2 (n = 19, 26.0%) or type 3 curve, respectively (n = 42, 57.5%). At multivariate analysis, the most predictive features for excluding presence of invasive disease were absence of enhancement or a type 1 curve on MRI (negative predictive value 98.5%; A{sub Z} 0.80, P = 0.00006). Contrast medium uptake kinetics at MRI provide high negative predictive value to exclude presence of invasion and may be useful in primary surgical planning in patients with a preoperative diagnosis of pure DCIS. (orig.)

  3. 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

  4. Non-Surgical Management of Ductal Dependent Lesion as a Safe Option: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Prem Alva

    2015-07-01

    Full Text Available Introduction: Critical congenital heart disease with ductal dependent pulmonary blood flow can present in early neonatal period as a cardiac emergency. Case Presentation: We herein reported a case of critical pulmonary stenosis in a newborn who presented with cyanosis and breathlessness. Conclusions: Initially managed with prostaglandin, an emergency balloon pulmonary valvuloplasty proved to be an effective and safe option.

  5. 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

  6. High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

    Science.gov (United States)

    Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B; Jansen, Sanaz A; Macleod, Kay; Conzen, Suzanne D; Karczmar, Gregory S

    2015-01-01

    The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (pcontrast media (pcontrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. 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...

  8. Variation in detection of ductal carcinoma in situ during screening mammography: a survey within the International Cancer Screening Network

    NARCIS (Netherlands)

    Lynge, E.; Ponti, A.; James, T.; Majek, O.; Euler-Chelpin, M. von; Anttila, A.; Fitzpatrick, P.; Frigerio, A.; Kawai, M.; Scharpantgen, A.; Broeders, M.J.; Hofvind, S.; Vidal, C.; Ederra, M.; Salas, D.; Bulliard, J.L.; Tomatis, M.; Kerlikowske, K.; Taplin, S.

    2014-01-01

    BACKGROUND: There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative

  9. “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...

  10. Telomere length alterations unique to invasive lobular carcinoma.

    Science.gov (United States)

    Heaphy, Christopher M; Asch-Kendrick, Rebecca; Argani, Pedram; Meeker, Alan K; Cimino-Mathews, Ashley

    2015-08-01

    Telomeres are nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes and protect chromosomal ends from degradation and recombination. Dysfunctional telomeres contribute to genomic instability, promote tumorigenesis, and, in breast cancer, have been associated with increased cancer risk and poor prognosis. Short telomere lengths have been previously associated with triple-negative and human epidermal growth factor receptor (Her2)--positive ductal carcinomas. However, these investigations have not specifically assessed invasive lobular carcinomas (ILCs), which accounts for 5% to 15% of all invasive breast cancers. Here, we evaluate telomere lengths within 48 primary ILCs with complete characterization of estrogen receptor (ER), progesterone receptor (PR), and Her2 status, including 32 luminal/Her2- (ER+/PR+/Her2-), 8 luminal/Her2+ (ER+/PR+/Her2+), 3 Her2+ (ER-/PR-/Her2+), and 5 triple-negative (ER-/PR-/Her2-) carcinomas. A telomere-specific fluorescence in situ hybridization assay, which provides single-cell telomere length resolution, was used to evaluate telomere lengths and compare with standard clinicopathological markers. In contrast to breast ductal carcinoma, in which more than 85% of cases display abnormally short telomeres, approximately half (52%) of the ILCs displayed either normal or long telomeres. Short telomere length was associated with older patient age. Interestingly, 3 cases (6%) displayed a unique telomere pattern consisting of 1 or 2 bright telomere spots among the normal telomere signals within each individual cancer cell, a phenotype that has not been previously described. Additional studies are needed to further evaluate the significance of the unique bright telomere spot phenotype and the potential utility of telomere length as a prognostic marker in ILC. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion.

    Science.gov (United States)

    Duivenvoorden, Hendrika M; Rautela, Jai; Edgington-Mitchell, Laura E; Spurling, Alex; Greening, David W; Nowell, Cameron J; Molloy, Timothy J; Robbins, Elizabeth; Brockwell, Natasha K; Lee, Cheok Soon; Chen, Maoshan; Holliday, Anne; Selinger, Cristina I; Hu, Min; Britt, Kara L; Stroud, David A; Bogyo, Matthew; Möller, Andreas; Polyak, Kornelia; Sloane, Bonnie F; O'Toole, Sandra A; Parker, Belinda S

    2017-12-01

    Mammography screening has increased the detection of early pre-invasive breast cancers, termed ductal carcinoma in situ (DCIS), increasing the urgency of identifying molecular regulators of invasion as prognostic markers to predict local relapse. Using the MMTV-PyMT breast cancer model and pharmacological protease inhibitors, we reveal that cysteine cathepsins have important roles in early-stage tumorigenesis. To characterize the cell-specific roles of cathepsins in early invasion, we developed a DCIS-like model, incorporating an immortalized myoepithelial cell line (N1ME) that restrained tumor cell invasion in 3D culture. Using this model, we identified an important myoepithelial-specific function of the cysteine cathepsin inhibitor stefin A in suppressing invasion, whereby targeted stefin A loss in N1ME cells blocked myoepithelial-induced suppression of breast cancer cell invasion. Enhanced invasion observed in 3D cultures with N1ME stefin A-low cells was reliant on cathepsin B activation, as addition of the small molecule inhibitor CA-074 rescued the DCIS-like non-invasive phenotype. Importantly, we confirmed that stefin A was indeed abundant in myoepithelial cells in breast tissue. Use of a 138-patient cohort confirmed that myoepithelial stefin A (cystatin A) is abundant in normal breast ducts and low-grade DCIS but reduced in high-grade DCIS, supporting myoepithelial stefin A as a candidate marker of lower risk of invasive relapse. We have therefore identified myoepithelial cell stefin A as a suppressor of early tumor invasion and a candidate marker to distinguish patients who are at low risk of developing invasive breast cancer, and can therefore be spared further treatment. 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.

  12. Non-invasive Detection of Breast Cancer Lymph Node Metastasis using Carbonic Anhydrases IX and XII Targeted Imaging Probes

    Science.gov (United States)

    Tafreshi, Narges K.; Bui, Marilyn M.; Bishop, Kellsey; Lloyd, Mark C.; Enkemann, Steven A.; Lopez, Alexis S.; Abrahams, Dominique; Carter, Bradford W.; Vagner, Josef; Grobmyer, Stephen R.; Gillies, Robert J.; Morse, David L.

    2014-01-01

    Purpose To develop targeted molecular imaging probes for the non-invasive detection of breast cancer lymph node metastasis. Methods Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry (IHC) of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX and CAXII specific monoclonal antibodies (mAbs) to a near-infrared fluorescent dye. Results Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice bearing mammary fat pad tumors of marker expressing cells, and non-expressing cells or by pre-injection of unlabeled antibody. Imaging of LN metastases showed that peritumorally-injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX and CAXII expressing cells into the axillary LNs. Conclusion These imaging probes have potential for non-invasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. PMID:22016510

  13. In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells

    Science.gov (United States)

    Liu, Tao; Wang, Chun-You; Yu, Feng; Gou, Shan-Miao; Wu, He-Shui; Xiong, Jiong-Xin; Zhou, Feng

    2007-01-01

    AIM: To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro. METHODS: Rat pancreatic tissue was submitted to digestion by collagenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XlHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulin-producing cells were detected by dithizone-staining. RESULTS: XlHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were significantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 ± 0.43 vs 3.48 ± 0.81, P < 0.01 at 5.6 mmol/L; 4.86 ± 1.15 vs 10.25 ± 1.32, P < 0.01 at 16.7 mmol/L). CONCLUSION: PDX-1 can differentiate rat pancreatic ductal epithelial cells into insulin-producing cells in vitro. In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells. PMID:17876894

  14. A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2.

    Science.gov (United States)

    Surmeli-Onay, Ozge; Yurdakok, Murat; Karagoz, Tevfik; Erkekoglu, Pinar; Ertugrul, Ilker; Takci, Sahin; Giray, Belma Kocer; Aykan, Hayrettin Hakan; Korkmaz, Ayse; Yigit, Sule

    2015-01-01

    Numerous investigations have demonstrated that phototherapy (PT) directly or indirectly causes ductal patency by photorelaxation effect. In this observational study, we aimed to assess the effect of PT on the incidence of patent ductus arteriosus (PDA) together with prostaglandins (PGE2) and (PGI2) levels in preterm infants. Preterm infants whose gestational age<34 weeks and who required PT in the first 3 d of life were enrolled in this prospective study. The clinical signs of PDA, the data of detailed echocardiographic study were recorded and plasma PGE2 and PGI2 levels were measured before and after PT. The outcome measures were the status of ductus arteriosus and alterations of PGE2 and PGI2 levels under the effect of PT. A total of 44 preterm infants were enrolled in the study, of these 21 (47.7%) were in Group 1 (Non-PDA Group) and 23 (52.3%) were in Group 2 (PDA Group). After PT, ductal reopening occurred in three infants (14.3%) in Group 1, while ductus closed in four infants in Group 2 (17.3%). PT does not seem to effect ductal patency for both groups (p=0.250 and p=0.125, respectively). PGE2 levels were not different before and after PT for both groups (p=0.087, p=0.408, respectively). However, PGI2 levels were significantly decreased after PT in both groups (p=0.006, and p=0.003, respectively). There was no effect of PT on ductal patency. We can conclude that PGs were eliminated simultaneously with ductal closure and photorelaxation effect did not influence PG levels.

  15. Attacking invasive grasses

    Science.gov (United States)

    Keeley, Jon E.

    2015-01-01

    In grasslands fire may play a role in the plant invasion process, both by creating disturbances that potentially favour non-native invasions and as a possible tool for controlling alien invasions. Havill et al. (Applied Vegetation Science, 18, 2015, this issue) determine how native and non-native species respond to different fire regimes as a first step in understanding the potential control of invasive grasses.

  16. HDAC2 promotes loss of primary cilia in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Kobayashi, Tetsuo; Nakazono, Kosuke; Tokuda, Mio; Mashima, Yu; Dynlacht, Brian David; Itoh, Hiroshi

    2017-02-01

    Loss of primary cilia is frequently observed in tumor cells, including pancreatic ductal adenocarcinoma (PDAC) cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction and the inability to exit the cell cycle. However, the molecular mechanisms that explain how PDAC cells lose primary cilia are still ambiguous. In this study, we found that inhibition or silencing of histone deacetylase 2 (HDAC2) restores primary cilia formation in PDAC cells. Inactivation of HDAC2 results in decreased Aurora A expression, which promotes disassembly of primary cilia. We further showed that HDAC2 controls ciliogenesis independently of Kras, which facilitates Aurora A expression. These studies suggest that HDAC2 is a novel regulator of primary cilium formation in PDAC cells. © 2016 The Authors.

  17. 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.

  18. A Silent Asymptomatic Solid Pancreas Tumor in a Nonsmoking Athletic Female: Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kyawzaw Lin

    2017-10-01

    Full Text Available A silent solid endocrine tumor of pancreas, intraductal adenocarcinoma of pancreas, is the fourth leading cancer-related death in the US. However, it is expected to become the third leading cause by 2030 owing to delayed diagnosis and slow progress in management. Chronic pancreatitis is at risk for pancreatic ductal adenocarcinoma (PDAC. PDAC is diagnostic with transabdominal sonogram, blood test such as carbohydrate antigen 19-9 (CA 19-9, and imaging. PDAC has a dismal prognosis. The survival rate in 5 years is barely 6%, while late detection rate is 80–85% with unresectable stage upon diagnosis. Here, we present a 51-year-old asymptomatic female with intermittent constipation and abdominal pain for 1 month with obstructive jaundice with PDAC with liver metastasis.

  19. Functions of pancreatic stellate cell-derived soluble factors in the microenvironment of pancreatic ductal carcinoma.

    Science.gov (United States)

    Wu, Qi; Tian, Ying; Zhang, Jingqiu; Zhang, Hongpeng; Gu, Fengming; Lu, Yongdie; Zou, Shengnan; Chen, Yuji; Sun, Pengxiang; Xu, Mengyue; Sun, Xiaoming; Xia, Chao; Chi, Hao; Ying Zhu, A; Tang, Dong; Wang, Daorong

    2017-11-24

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer with poor prognosis because it is highly resistant to traditional chemotherapy and radiotherapy and it has a low rate of surgical resection eligibility. Pancreatic stellate cells (PSC) have become a research hotspot in recent years, and play a vital role in PDAC microenvironment by secreting soluble factors such as transforming growth factor β, interleukin-6, stromal cell-derived factor-1, hepatocyte growth factor and galectin-1. These PSC-derived cytokines and proteins contribute to PSC activation, participating in PDAC cell proliferation, migration, fibrosis, angiogenesis, immunosuppression, epithelial-mesenchymal transition, and chemoradiation resistance, leading to malignant outcome. Consequently, targeting these cytokines and proteins or their downstream signaling pathways is promising for treating PDAC.

  20. 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...

  1. 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.

  2. Metastatic Infiltrating Ductal Carcinoma of the Breast to the Colon: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Salih Samo

    2013-01-01

    Full Text Available True metastatic involvement of the colon is rare. Colonic metastases occur most commonly secondary to peritoneal metastases from intra-abdominal malignancies. Breast cancer is the most common malignancy that metastasizes hematogenously to the colon. Colonic metastatic disease mimics primary colonic tumors in its presentation. Colonic metastatic involvement is a poor prognostic sign, and the pathologist should be informed about the history of the primary breast cancer when examining the pathologic specimens. In this paper, we report a case of an ileocecal mass found to be histologically consistent with metastatic ductal breast cancer, and then we review the literature about breast cancer metastases to the gastrointestinal tract in general and colon in particular.

  3. Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review

    Science.gov (United States)

    Paiella, Salvatore; Salvia, Roberto; Ramera, Marco; Girelli, Roberto; Frigerio, Isabella; Giardino, Alessandro; Allegrini, Valentina; Bassi, Claudio

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures. PMID:26981115

  4. Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine.

    Science.gov (United States)

    Knudsen, Erik S; O'Reilly, Eileen M; Brody, Jonathan R; Witkiewicz, Agnieszka K

    2016-01-01

    Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. 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.

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

    Science.gov (United States)

    Pitarresi, Jason R; Liu, Xin; Sharma, Sudarshana M; Cuitiño, 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; Rosol, Thomas J; Shakya, Reena; Ludwig, Thomas; Lesinski, Gregory B; Fernandez, Soledad A; Konieczny, Stephen F; Leone, Gustavo; Wu, Jinghai; Ostrowski, Michael C

    2016-09-01

    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 samples relative to normal pancreatic controls. LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) mice showed that ETS2 expression initially increased in fibroblasts during ADM and remained elevated through progression to PDAC. Conditional ablation of Ets-2 in pancreatic fibroblasts in a Kras(G12D)-driven mouse ADM model decreased the amount of ADM events. ADMs from fibroblast Ets-2-deleted animals had reduced epithelial cell proliferation and increased apoptosis. Surprisingly, fibroblast Ets-2 deletion significantly altered immune cell infiltration into the stroma, with an increased CD8+ T-cell population, and decreased presence of regulatory T cells (Tregs), myeloid-derived suppressor cells, and mature macrophages. The mechanism involved ETS2-dependent chemokine ligand production in fibroblasts. ETS2 directly bound to regulatory sequences for Ccl3, Ccl4, Cxcl4, Cxcl5, and Cxcl10, a group of chemokines that act as potent mediators of immune cell recruitment. These results suggest an unappreciated role for ETS2 in fibroblasts in establishing an immune-suppressive microenvironment in response to oncogenic Kras(G12D) signaling during the initial stages of tumor development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia.

    Science.gov (United States)

    Greer, Renee L; Staley, Binnaz K; Liou, Angela; Hebrok, Matthias

    2013-11-01

    Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer-related death. Through the process of acinar-to-ductal metaplasia (ADM), pancreatic acinar cells give rise to pancreatic intraepithelial neoplasia (PanIN), the most common precursor of PDA. However, even when Kras is activated in a majority of acinar cells, ADM and subsequent development of PanINs is inefficient in the absence of additional stresses. Numb regulates cell junctions, integrins, and the activity of embryonic signaling pathways; therefore, we investigated its effects on acinar cell dedifferentiation, regeneration, and metaplasia. We used mouse models of pancreatic regeneration and PDA as well as mice with loss-of-function alleles of Numb (p48Cre/p48Cre(ER);Numb(f/f) and p48Cre/p48Cre(ER);Kras(G12D);Numb(f/f) mice) to study the roles of Numb in pancreatic regeneration and ADM. Loss of Numb resulted in premature dedifferentiation of acinar cells in response to injury due to administration of the cholecystokinin analogue cerulein and interfered with acinar cell regeneration. Numb was found to regulate multiple signaling pathways in acinar cells during cerulein-induced pancreatitis. Disruption of Numb accelerated and destabilized ADM in the context of oncogenic Kras (in p48Cre;Kras(G12D);Numb(f/f) and p48Cre(ER);Kras(G12D);Numb(f/f) mice). Numb is an important regulator of acinar cell differentiation and viability during metaplasia. In mice with pancreatitis or pancreatic injury, elimination of Numb causes dedifferentiated acinar cells to undergo apoptosis, and this is not mitigated by oncogenic Kras. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  8. Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells.

    Science.gov (United States)

    Simsek, Senem; Zhou, Ting; Robinson, Christopher L; Tsai, Su-Yi; Crespo, Miguel; Amin, Sadaf; Lin, Xiangyi; Hon, Jane; Evans, Todd; Chen, Shuibing

    2016-05-01

    We established an efficient strategy to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell (iPSC) line derived from patients with cystic fibrosis, to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. In addition, iPSC lines were derived from a patient with CF carrying compound frameshift and mRNA splicing mutations and were differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCCF)-iPSCs showed defective expression of mature CFTR protein and impaired chloride ion channel activity, recapitulating functional defects of patients with CF at the cellular level. These studies provide a new methodology to derive pure PDECs expressing CFTR and establish a "disease in a dish" platform to identify drug candidates to rescue the pancreatic defects of patients with CF. An efficient strategy was established to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell line derived from patients with cystic fibrosis (CF-iPSCs), to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-PDECs derived from CF-iPSCs showed defective expression of mature cystic fibrosis transmembrane conductance regulator (CFTR) protein and impaired chloride ion channel activity, recapitulating functional pancreatic defects of patients with CF at the cellular level. These studies provide a new methodology for deriving pure PDECs expressing CFTR, and they establish a "disease-in-a-dish" platform for identifying drug candidates to rescue the pancreatic defects of these patients. ©AlphaMed Press.

  9. Mammographic findings of infiltrating ductal carcinoma: correlation with histologic grading and age

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kue Hee; Lee, Ki Yeol; Kang, Eun Young [Korea Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-11-01

    To investigate the correlation between mammographic findings of infiltrating ductal carcinoma (IDC), patient age and pathologic grading. The study included 103 cases of infiltrating ductal carcinoma in 102 women who during the preceding three years had undergone mammography and surgery. The mammograms were retrospectively reviewed by two radiologists. The mean age of the patients was 45.2 (range 26 - 74) years and the age distribution was seven in the 3rd decade, 37 in the 4th, 29 in the 5th, 24 in the 6th, and six in the 7th or above. Thirty-three lesions were histologic. Grade 1, 59 were Grade 2 and 11 were Grade 3. Ten (9.7%) of 103 cases, all of whom were younger than 50, were missed during mammographic diagnosis. On mammograms, primary findings of breast malignancy were found in 54 (74%) of 73 patients younger than 50 and 27 (90%) of 30 patients older than 51. Mass with or without microcalcification was found in 45 patients (62%) younger than 50 and in 26 (87%) older than 51. Nine (12%) and 3 (10%) in each age group showed secondary findings. There was no correlation between age distribution and histologic grading. Seventy-three percent of Grade 1 lesions and 78% of those of Grade 3 showed primary findings. Five lesions in each of Grade 1 and 2 were missed at mammographic interpretation, but this was not statistically significant (p=0.250). In all 11 Grade 3 cases, breast cancer were manifested as primary findings, but this was not statistically significant (p=0.203). The majority of IDC were detected by mammography, but 9.7% of IDC patients, all younger than 50, were misdiagnosed. Most IDC was manifested as primary findings, particularly in patients aged over 51. There were no differences in pathologic grading according to age distribution. All histologic Grade 3 lesions were detected by mammography.

  10. Trypsin Reduces Pancreatic Ductal Bicarbonate Secretion by Inhibiting CFTR Cl- channel and Luminal Anion Exchangers

    Science.gov (United States)

    Pallagi, Petra; Venglovecz, Viktória; Rakonczay, Zoltán; Borka, Katalin; Korompay, Anna; Ózsvári, Béla; Judák, Linda; Sahin-Tóth, Miklós; Geisz, Andrea; Schnúr, Andrea; Maléth, József; Takács, Tamás; Gray, Mike A.; Argent, Barry E.; Mayerle, Julia; Lerch, Markus M.; Wittmann, Tibor; Hegyi, Péter

    2012-01-01

    Background & Aims The effects of trypsin on pancreatic ductal epithelial cells (PDEC) vary among species and depend on localization of proteinase-activated receptor-2 (PAR-2). Bicarbonate secretion is similar in human and guinea pig PDEC; we compared its localization in these cell types and isolated guinea pig ducts to study the effects of trypsin and a PAR-2 agonist on this process. Methods PAR-2 localization was analyzed by immunohistochemistry in guinea pig and human pancreatic tissue samples (from 15 patients with chronic pancreatitis and 15 without pancreatic disease). Functions of guinea pig PDEC were studied by microperfusion of isolated ducts, measurements of intracellular pH (pHi) and Ca2+ concentration [Ca2+]i, and patch clamp analysis. The effect of pH on trypsinogen autoactivation was assessed using recombinant human cationic trypsinogen. Results PAR-2 localized to the apical membrane of human and guinea pig PDEC. Trypsin increased [Ca2+]i and pHi, and inhibited secretion of bicarbonate by the luminal anion exchanger and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Autoactivation of human cationic trypsinogen accelerated when the pH was reduced from 8.5 to 6.0. PAR-2 expression was strongly down-regulated, at transcriptional and protein levels, in the ducts of patients with chronic pancreatitis, consistent with increased activity of intraductal trypsin. Importantly, in PAR-2 knockout mice, the effects of trypsin were PAR-2 dependent. Conclusions Trypsin reduces pancreatic ductal bicarbonate secretion via PAR-2–dependent inhibition of the apical anion exchanger and the CFTR Cl- channel. This could contribute to the development of chronic pancreatitis, decreasing luminal pH and promoting premature activation of trypsinogen in the pancreatic ducts. PMID:21893120

  11. Ductal carcinoma In-Situ in turner syndrome patient undergoing hormone replacement therapy: A case report

    Directory of Open Access Journals (Sweden)

    Rashmi Bawa

    2016-03-01

    Full Text Available Turner’s syndrome is a rare congenital disease which affects about 1 in every 2500-3000 live-born females. This happens due to chromosomal abnormalities in a phenotypic female, causing increased gonadotropin concentrations and low concentrations of estrogens from infancy. As a result, hormone replacement therapy is started in most adolescent Turner syndrome patients to initiate and sustain sexual maturation. Accordingly, most Turner’s syndrome patients undergo several decades of estrogen replacement therapy, from puberty to post-menopausal age. The highly publicized findings of the Women’s Health Initiative have called into question the appropriateness of hormone replacement therapy in adolescents with Turner’s syndrome. Those concerns were mostly theoretical extrapolations, as few prospective studies of cancer occurrence in women with Turner syndrome have been reported. Consequently, several recent publications have challenged those extrapolations, based on the assertion that the levels of hormone replacement in Turner syndrome patients are well below the physiologic levels observed in normal menstruating women, as well as the fact that these women are significantly younger than those studied by the Women’s Health Initiative. In discord to those reports, we present a case of ductal carcinoma in-situ in a 40-year-old Turner patient, who had undergone over two decades of combined hormone replacement therapy. The patient underwent an elective excisional biopsy for a palpable mass, with histopathology revealing a complex fibroadenoma with a nidus of ductal carcinoma in-situ. The lesion was noted to be estrogen receptor positive and progesterone receptor negative, with heavy staining for HER-2/Neu receptor. The patient was treated with tamoxifen. While a rare case, it is imperative for the astute clinician to keep in mind the consequences of long-term hormone replacement therapy in Turner’s syndrome patients in order to avoid missed

  12. The prognostic value of tumor budding in invasive breast cancer.

    Science.gov (United States)

    Liang, Fenli; Cao, Wei; Wang, Yili; Li, Linrui; Zhang, Guanjun; Wang, Zhuo

    2013-05-01

    We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (Pbudded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, Ptumor size (HR 2.468, P=0.002), node status (HR 2.362, Ptumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Risk factors for young-onset invasive and in situ breast cancer.

    Science.gov (United States)

    O'Brien, Katie M; Sun, Jenny; Sandler, Dale P; DeRoo, Lisa A; Weinberg, Clarice R

    2015-12-01

    Young-onset breast cancers tend to be more aggressive than later-onset tumors and may have different risk factor profiles. Among young-onset cases, there may also be etiologic differences between ductal carcinomas in situ (DCIS) and invasive breast cancer, particularly if some factors promote malignant transformation. We evaluated the association between several potential risk factors and young-onset breast cancer in the Two Sister Study (2008-2010), a sister-matched case-control study involving 1,406 women diagnosed with breast cancer before age 50 (1,185 invasive, 221 DCIS) and 1,648 controls. Older age at menarche, younger age at menopause, premenopausal hysterectomy, early age at first-term pregnancy, obesity, and consumption of alcohol were associated with reduced risk of young-onset breast cancer. These patterns remained when we limited analysis to invasive breast cancers. In general, effect estimates were similar for young-onset invasive breast cancer and DCIS, although the number of DCIS cases was small. In this sister-matched case-control study of young-onset breast cancer, many of the studied risk factors were associated with young-onset invasive breast cancer. There were few discernable differences in risk factors for young-onset DCIS versus young-onset invasive breast cancer.

  14. In-situ and invasive carcinoma within a phyllodes tumor associated with lymph node metastases

    Directory of Open Access Journals (Sweden)

    Ross Joan

    2004-12-01

    Full Text Available Abstract Background Phyllodes tumors (cystosarcoma phyllodes are uncommon lesions in the female breast. Rarely, the occurrence of carcinoma within a phyllodes tumor has been reported in the literature, but has never been associated with lymph node metastases. Case presentation A 26-year-old woman presented with a firm, mobile, non-tender mass in the left breast and palpable lymph nodes in the left axilla. The excised lesion appeared well circumscribed and lobulated, with variable fleshy and firm areas. Microscopic examination showed a circumscribed fibroepithelial lesion with a well developed leaf-like architecture, in keeping with a benign phyllodes tumor. The epithelial component showed extensive high grade ductal carcinoma in-situ (DCIS and invasive carcinoma of no special type, located entirely within the phyllodes tumor. Subsequent axillary lymph node dissection revealed metastatic carcinoma in four lymph nodes. Conclusions Although rare, phyllodes tumors may harbor DCIS and invasive carcinoma, with potential for lymph node metastasis.

  15. 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.

  16. ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

    Science.gov (United States)

    Chronopoulos, Antonios; Robinson, Benjamin; Sarper, Muge; Cortes, Ernesto; Auernheimer, Vera; Lachowski, Dariusz; Attwood, Simon; García, Rebeca; Ghassemi, Saba; Fabry, Ben; del Río Hernández, Armando

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC. PMID:27600527

  17. Invasion-promoting extracellular matrix composition enhances photodynamic therapy response in 3D pancreatic cancer models

    Science.gov (United States)

    Cramer, Gwendolyn M.; El-Hamidi, Hamid; Celli, Jonathan P.

    2017-02-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by extracellular matrix-rich stromal involvement, but it is not clear how ECM properties that affect invasiveness and chemotherapy response influence efficacy of photodynamic therapy (PDT). To disentangle the mechanical and biochemical effects of ECM composition, we measured the effects of various combinations of ECM proteins on growth behavior, invasive potential, and therapeutic response of multicellular 3D pancreatic tumor models. These spheroids were grown in attachment-free conditions before embedding in combinations of rheologically characterized collagen 1 and Matrigel combinations and treated with oxaliplatin chemotherapy and PDT. We find that cells invading from collagen-embedded tumor spheroids, the least rigid ECM substrate described here, displayed better response to PDT than to oxaliplatin chemotherapy. Overall, our results support that ECM-mediated invading PDAC populations remain responsive to PDT in conditions that induce chemoresistance.

  18. Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.

    Science.gov (United States)

    Jacobs, Carmel; Clemons, Mark; Addison, Christina; Robertson, Susan; Arnaout, Angel

    2016-01-01

    Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC. © 2015 Wiley Periodicals, Inc.

  19. Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma.

    Science.gov (United States)

    Basturk, Olca; Berger, Michael F; Yamaguchi, Hiroshi; Adsay, Volkan; Askan, Gokce; Bhanot, Umesh K; Zehir, Ahmet; Carneiro, Fatima; Hong, Seung-Mo; Zamboni, Giuseppe; Dikoglu, Esra; Jobanputra, Vaidehi; Wrzeszczynski, Kazimierz O; Balci, Serdar; Allen, Peter; Ikari, Naoki; Takeuchi, Shoko; Akagawa, Hiroyuki; Kanno, Atsushi; Shimosegawa, Tooru; Morikawa, Takanori; Motoi, Fuyuhiko; Unno, Michiaki; Higuchi, Ryota; Yamamoto, Masakazu; Shimizu, Kyoko; Furukawa, Toru; Klimstra, David S

    2017-12-01

    Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing. Three of these intraductal tubulopapillary neoplasms were also subjected to whole-genome sequencing. All intraductal tubulopapillary neoplasms revealed the characteristic histologic (cellular intraductal nodules of back-to-back tubular glands lined by predominantly cuboidal cells with atypical nuclei and no obvious intracellular mucin) and immunohistochemical (immunolabeled with MUC1 and MUC6 but were negative for MUC2 and MUC5AC) features. By genomic analyses, there was loss of CDKN2A in 5/20 (25%) of these cases. However, the majority of the previously reported intraductal papillary mucinous neoplasm-related alterations were absent. Moreover, in contrast to most ductal neoplasms of the pancreas, MAP-kinase pathway was not involved. In fact, 2/22 (9%) of intraductal tubulopapillary neoplasms did not reveal any mutations in the tested genes. However, certain chromatin remodeling genes (MLL1, MLL2, MLL3, BAP1, PBRM1, EED, and ATRX) were found to be mutated in 7/22 (32%) of intraductal tubulopapillary neoplasms and 27% harbored phosphatidylinositol 3-kinase (PI3K) pathway (PIK3CA, PIK3CB, INPP4A, and PTEN) mutations. In addition, 4/18 (18%) of intraductal tubulopapillary neoplasms had FGFR2

  20. Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data

    Science.gov (United States)

    2012-01-01

    Background Molecular studies of breast cancer revealed biological heterogeneity of the disease and opened new perspectives for personalized therapy. While multiple gene expression-based systems have been developed, current clinical practice is largely based upon conventional clinical and pathologic criteria. This gap may be filled by development of combined multi-IHC indices to characterize biological and clinical behaviour of the tumours. Digital image analysis (DA) with multivariate statistics of the data opens new opportunities in this field. Methods Tissue microarrays of 109 patients with breast ductal carcinoma were stained for a set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16). Aperio imaging platform with the Genie, Nuclear and Membrane algorithms were used for the DA. Factor analysis of the DA data was performed in the whole group and hormone receptor (HR) positive subgroup of the patients (n = 85). Results Major factor potentially reflecting aggressive disease behaviour (i-Grade) was extracted, characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α. The i-Grade factor scores revealed bimodal distribution and were strongly associated with higher Nottingham histological grade (G) and more aggressive intrinsic subtypes. In HR-positive tumours, the aggressiveness of the tumour was best defined by positive Ki67 and negative ER loadings. High Ki67/ER factor scores were strongly associated with the higher G and Luminal B types, but also were detected in a set of G1 and Luminal A cases, potentially indicating high risk patients in these categories. Inverse relation between HER2 and PR expression was found in the HR-positive tumours pointing at differential information conveyed by the ER and PR expression. SATB1 along with HIF-1α reflected the second major factor of variation in our patients; in the HR-positive group they were inversely associated with the HR and BCL2 expression and represented the major factor of

  1. Immunohistochemistry profiles of breast ductal carcinoma: factor analysis of digital image analysis data

    Directory of Open Access Journals (Sweden)

    Laurinavicius Arvydas

    2012-03-01

    Full Text Available Abstract Background Molecular studies of breast cancer revealed biological heterogeneity of the disease and opened new perspectives for personalized therapy. While multiple gene expression-based systems have been developed, current clinical practice is largely based upon conventional clinical and pathologic criteria. This gap may be filled by development of combined multi-IHC indices to characterize biological and clinical behaviour of the tumours. Digital image analysis (DA with multivariate statistics of the data opens new opportunities in this field. Methods Tissue microarrays of 109 patients with breast ductal carcinoma were stained for a set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16. Aperio imaging platform with the Genie, Nuclear and Membrane algorithms were used for the DA. Factor analysis of the DA data was performed in the whole group and hormone receptor (HR positive subgroup of the patients (n = 85. Results Major factor potentially reflecting aggressive disease behaviour (i-Grade was extracted, characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α. The i-Grade factor scores revealed bimodal distribution and were strongly associated with higher Nottingham histological grade (G and more aggressive intrinsic subtypes. In HR-positive tumours, the aggressiveness of the tumour was best defined by positive Ki67 and negative ER loadings. High Ki67/ER factor scores were strongly associated with the higher G and Luminal B types, but also were detected in a set of G1 and Luminal A cases, potentially indicating high risk patients in these categories. Inverse relation between HER2 and PR expression was found in the HR-positive tumours pointing at differential information conveyed by the ER and PR expression. SATB1 along with HIF-1α reflected the second major factor of variation in our patients; in the HR-positive group they were inversely associated with the HR and BCL2 expression and represented

  2. A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients

    Directory of Open Access Journals (Sweden)

    Wang Q

    2016-09-01

    Full Text Available Qingbing Wang,1,2 Xiaolin Wang,1,2 Rongfang Guo,2,3 Guoping Li1,2 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, 2Shanghai Institute of Medical Imaging, 3Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Pancreatic acinar cell carcinoma (ACC is a rare tumor that is difficult to diagnose preoperatively. The aim of this study was to evaluate and describe the computed tomography (CT features of ACC and compare the results with pancreatic ductal adenocarcinoma (DAC for improving preoperative diagnosis. The control group consisted of 34 patients with DAC collected from the pathology electronic database. The CT imaging from nine patients with pathologically confirmed ACC was retrospectively reviewed. Two radiologists independently assessed the tumor location, size, texture, and enhancement patterns. We found that 64.3% (9/14 of ACC tumors were homogeneous and 35.7% (5/14 had necrosis. The percentage of common bile duct and pancreatic ductal dilation was 14.3% (2/14 and 7.1% (1/14, respectively. The mean size of ACC was 50.1±24.2 mm. The mean attenuation of ACC was 35.4±3.9 Hounsfield unit (HU before enhancement, 73.1±42.9 HU in arterial phase, and 71.8±15.6 HU in port venous phase. It is difficult to distinguish ACC from DAC preoperatively only based on CT findings. However, compared with DAC, we found that ACC tumors are likely to be larger and contain more heterogeneous intratumoral necrotic hypovascular regions, and less pancreatic ductal and common biliary dilation. Keywords: acinar cell carcinoma, computed tomography, pancreatic ductal carcinoma, pancreas

  3. 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.

  4. [Detection of invasive breast lobular carcinoma by image analysis: comparison between mammography and ultrasound].

    Science.gov (United States)

    López-Narváez, Ricardo A; Garza-Montemayor, Margarita L; Garza-García, Nancy L; Ojeda-Mendez, Erik E; Rangel-Nava, Hugo; Méndez-Lozano, Daniel; Morales-Caballero, Fidel G

    2012-05-01

    Early detection of lobular cancer has for long implied a challenge for diagnostic imaging due to the peculiar histology it presents that makes clinical and radiology detection rather difficult. The aim of our study was to compare the sensitivity and specificity of mammography and ultrasound for the diagnosis of invasive breast lobular carcinoma. This is a retrospective study of women with histopathological diagnosis of invasive breast lobular carcinoma in the period between September 2006 and August 2009. All patients underwent mammography and ultrasound. The final pathology report was used as reference standard and the sensitivity and specificity of mammography and ultrasound were evaluated statistically using chi-square test (chi2). The analysis included 654 patients who underwent biopsy. Among them, 148 (22.62%) were positive and 506 (77.37%) negative for cancer. The average age was 48 years (range 18-89). The sensitivity of ultrasound was higher in the group of invasive lobular cancer (ILC) in 14/14 (100%) cases, in contrast to 87/111 (78%) cases of invasive ductal carcinoma (IDC) and 9/18 (50 %) cases of ductal carcinoma in situ (DCIS). The mammography showed greater sensitivity in the group of DCIS in 17/18 (94%) cases, unlike 9/14 (64%) cases of ILC and 89/111 (80%) cases of IDC. Ultrasound improves the detection of ILC with sensitivity up to 100% compared to 64% by mammography. The combination of both diagnostic tests showed sensitivity equal to the ultrasound, but it decreased 30% the specificity in this group.

  5. 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.

  6. Ductal Adenocarcinoma: A Rare Entity of Prostate Gland in a Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Patient

    Directory of Open Access Journals (Sweden)

    Tumay Ozgur

    2016-02-01

    Full Text Available Prostate cancer is the most common malignancy in men and ductal adenocarcinoma is a pathologic subtype with specific histological and clinical features. Seventy-six year-old male patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL admitted to our hospital with lower urinary tract symptoms. The last prostate specific antigen (PSA level was 26 ng/ml and serial transrectal ultrasound guided biopsies were administered and benign prostate hyperplasia and non-specific prostatitis were the results of pathology reports. Due to the persistence of the symptoms transurethral resection of the prostate was performed. In the pathologic evaluation of the material adenocarcinoma focuses without stroma has been observed between the hyperplasic prostate tissues. The tumor has been diagnosed as ductal adenocarcinoma with 4+4 Gleason pattern score. Bone scintigraphy was revealed activity uptake on lomber vertebral column due to metastasis. Computerized tomography was revealed previous bilateral inguinal and right iliac lymphadenopathy due to CLL/SLL. Total androgen deprivation therapy and bilateral orchiectomy was applied. After three mounts according to biochemical and imaging results,  radiotherapy cure began. Ductal adenocarcinoma is a rare subtype of prostate carcinoma with clinical behavior from that seen in conventional adenocarcinoma. On the other hand it is worth to point out the occurence of this entity as second malignancy during follow-up of CLL/SLL.

  7. 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.

  8. Attenuation of hedgehog acyltransferase-catalyzed sonic Hedgehog palmitoylation causes reduced signaling, proliferation and invasiveness of human carcinoma cells

    DEFF Research Database (Denmark)

    Konitsiotis, Antonios D; Chang, Shu-Chun; Jovanović, Biljana

    2014-01-01

    autocrine and juxtacrine signaling, and inhibited PDAC cell growth and invasiveness in vitro. In addition, Hhat knockdown in a HEK293a cell line constitutively expressing Shh and A549 human non-small cell lung cancer cells inhibited their ability to signal in a juxtacrine/paracrine fashion to the reporter......Overexpression of Hedgehog family proteins contributes to the aetiology of many cancers. To be highly active, Hedgehog proteins must be palmitoylated at their N-terminus by the MBOAT family multispanning membrane enzyme Hedgehog acyltransferase (Hhat). In a pancreatic ductal adenocarcinoma (PDAC...

  9. Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma

    Science.gov (United States)

    Kuo, Kung-Kai; Kuo, Chao-Jen; Chiu, Chiang-Yen; Liang, Shih-Shin; Huang, Chun-Hao; Chi, Shu-Wen; Tsai, Kun-Bow; Chen, Chiao-Yun; Hsi, Edward; Cheng, Kuang-Hung; Chiou, Shyh-Horng

    2016-01-01

    Objectives The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling. Methods Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion. Results Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, ≥2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include α-enolase, α-catenin, 14-3-3 β, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining. Conclusions The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC. PMID:26262590

  10. Antiproliferative effects and mechanisms of liver X receptor ligands in pancreatic ductal adenocarcinoma cells.

    Science.gov (United States)

    Candelaria, Nicholes R; Addanki, Sridevi; Zheng, Jine; Nguyen-Vu, Trang; Karaboga, Husna; Dey, Prasenjit; Gabbi, Chiara; Vedin, Lise-Lotte; Liu, Ka; Wu, Wanfu; Jonsson, Philip K; Lin, Jean Z; Su, Fei; Bollu, Lakshmi Reddy; Hodges, Sally E; McElhany, Amy L; Issazadeh, Mehdi A; Fisher, William E; Ittmann, Michael M; Steffensen, Knut R; Gustafsson, Jan-Åke; Lin, Chin-Yo

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-related malignancies. Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol homeostasis, lipid metabolism, and inflammation, and LXR agonists have been developed to regulate LXR function in these processes. Intriguingly, these compounds also exhibit antiproliferative activity in diverse types of cancer cells. In this study, LXR agonist treatments disrupted proliferation, cell-cycle progression, and colony-formation of PDAC cells. At the molecular level, treatments downregulated expression of proteins involved in cell cycle progression and growth factor signaling. Microarray experiments further revealed changes in expression profiles of multiple gene networks involved in biological processes and pathways essential for cell growth and proliferation following LXR activation. These results establish the antiproliferative effects of LXR agonists and potential mechanisms of action in PDAC cells and provide evidence for their potential application in the prevention and treatment of PDAC.

  11. Antiproliferative effects and mechanisms of liver X receptor ligands in pancreatic ductal adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Nicholes R Candelaria

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-related malignancies. Liver X receptors (LXRs are nuclear receptors that regulate cholesterol homeostasis, lipid metabolism, and inflammation, and LXR agonists have been developed to regulate LXR function in these processes. Intriguingly, these compounds also exhibit antiproliferative activity in diverse types of cancer cells. In this study, LXR agonist treatments disrupted proliferation, cell-cycle progression, and colony-formation of PDAC cells. At the molecular level, treatments downregulated expression of proteins involved in cell cycle progression and growth factor signaling. Microarray experiments further revealed changes in expression profiles of multiple gene networks involved in biological processes and pathways essential for cell growth and proliferation following LXR activation. These results establish the antiproliferative effects of LXR agonists and potential mechanisms of action in PDAC cells and provide evidence for their potential application in the prevention and treatment of PDAC.

  12. Predictors and Diagnostic Strategies for Early-Stage Pancreatic Ductal Adenocarcinoma: A Retrospective Study.

    Science.gov (United States)

    Kimura, Hideyo; Ohtsuka, Takao; Matsunaga, Taketo; Watanabe, Yusuke; Tamura, Koji; Ideno, Noboru; Aso, Teppei; Miyazaki, Tetsuyuki; Osoegawa, Takashi; Aishima, Shinichi; Miyasaka, Yoshihiro; Ueda, Junji; Ushijima, Yasuhiro; Igarashi, Hisato; Ito, Tetsuhide; Takahata, Shunichi; Oda, Yoshinao; Mizumoto, Kazuhiro; Tanaka, Masao

    2015-10-01

    As a strategy to diagnose early-stage pancreatic ductal adenocarcinoma (PDAC) is urgently needed, we aimed to clarify characteristics of early-stage PDAC. We retrospectively reviewed medical records of 299 consecutive patients who underwent R0 or R1 surgical resection for PDAC between 1994 and 2013 and compared clinical characteristics between patients with early-stage (stages 0-I by Japanese General Rules for Pancreatic Cancer) and advanced-stage (stages II-IV) disease. Diagnostic processes were also analyzed. Twenty-four patients (8%) had early-stage PDAC (stage 0: 11; stage I: 13). Univariate and multivariate analyses showed that presence or history of intraductal papillary mucinous neoplasm (P early-stage PDAC. Cytological examination during endoscopic retrograde pancreatography cytology was ∼65% sensitive in preoperative diagnosis of early-stage PDAC, whereas other imaging modalities were only 29% to 38% sensitive; 9 of 24 early-stage PDACs were diagnosed by endoscopic retrograde pancreatography cytology alone. Endoscopic retrograde pancreatography cytology for patients with intraductal papillary mucinous neoplasm or pancreatitis may help diagnose early-stage PDAC. Surveillance of extrapancreatic malignancies might also provide opportunities to detect early-stage PDAC as a second malignancy.

  13. Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Dung-Tsa Chen

    Full Text Available The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63 was used with overall survival (OS as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102. Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001 and Stratford et al cohort (HR = 2.07; p = 0.02, and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts. In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients.

  14. Treatment outcome of ductal carcinoma in situ patients treated with postoperative radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yu Jin; Kim, Kyu Bo; Choi, Eui Kyu; Han, Won Shik; Noh, Dong Young; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the outcome of ductal carcinoma in situ (DCIS) patients who underwent surgery followed by radiation therapy (RT). We retrospectively reviewed 106 DCIS patients who underwent surgery followed by postoperative RT between 1994 and 2006. Ninety-four patients underwent breast-conserving surgery, and mastectomy was performed in 12 patients due to extensive DCIS. Postoperative RT was delivered to whole breast with 50.4 Gy/28 fx. Tumor bed boost was offered to 7 patients (6.6%). Patients with hormonal receptor-positive tumors were treated with hormonal therapy. The median follow-up duration was 83.4 months (range, 33.4 to 191.5 months) and the median age was 47.8 years. Ten patients (9.4%) had resection margin <1 mm and high-grade and estrogen receptor-negative tumors were observed in 39 (36.8%) and 20 (18.9%) patients, respectively. The 7-year ipsilateral breast tumor recurrence (IBTR)-free survival rate was 95.3%. Resection margin (<1 or ≥1 mm) was the significant prognostic factor for IBTR in univariate and multivariate analyses (p < 0.001 and p = 0.016, respectively). Postoperative RT for DCIS can achieve favorable treatment outcome. Resection margin was the important prognostic factor for IBTR in the DCIS patients who underwent postoperative RT.

  15. Vesicular stomatitis virus as an oncolytic agent against pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Murphy, Andrea M; Besmer, Dahlia M; Moerdyk-Schauwecker, Megan; Moestl, Natascha; Ornelles, David A; Mukherjee, Pinku; Grdzelishvili, Valery Z

    2012-03-01

    Vesicular stomatitis virus (VSV) is a promising oncolytic agent against a variety of cancers. However, it has never been tested in any pancreatic cancer model. Pancreatic ductal adenocarcinoma (PDA) is the most common and aggressive form of pancreatic cancer. In this study, the oncolytic potentials of several VSV variants were analyzed in a panel of 13 clinically relevant human PDA cell lines and compared to conditionally replicative adenoviruses (CRAds), Sendai virus and respiratory syncytial virus. VSV variants showed oncolytic abilities superior to those of other viruses, and some cell lines that exhibited resistance to other viruses were successfully killed by VSV. However, PDA cells were highly heterogeneous in their susceptibility to virus-induced oncolysis, and several cell lines were resistant to all tested viruses. Resistant cells showed low levels of very early VSV RNA synthesis, indicating possible defects at initial stages of infection. In addition, unlike permissive PDA cell lines, most of the resistant cell lines were able to both produce and respond to interferon, suggesting that intact type I interferon responses contributed to their resistance phenotype. Four cell lines that varied in their permissiveness to VSV-ΔM51 and CRAd dl1520 were tested in mice, and the in vivo results closely mimicked those in vitro. While our results demonstrate that VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance of some PDAs to oncolytic virotherapy.

  16. Proposed classification of the feline "complex" mammary tumors as ductal and intraductal papillary mammary tumors.

    Science.gov (United States)

    Zappulli, V; Caliari, D; Rasotto, R; Ferro, S; Castagnaro, M; Goldschmidt, M

    2013-11-01

    When compared with the canine species, feline mammary tumors (FMTs) are much less heterogeneous, with a predominance of simple malignant neoplasm. Benign FMTs are rare, and it is unclear if complex and mixed tumors exist in the feline. In this study, we selected for immunohistochemical analyses 12 FMTs that had unusual histologic features. A group of 8 (2 benign and 6 malignant) FMTs showed a biphasic epithelial/myoepithelial population and a very regular cord-like distribution in a "Chinese lettering" pattern, within ectatic ducts. A second group (2 benign and 2 malignant) had an intraductal epithelial papillary growth pattern with a basally located monolayer of myoepithelial cells and a supporting fibrovascular stroma. The myoepithelial component always produced a standard immunohistochemical signature. All malignancies were grade I, and the subjects were all alive at 1 year postdiagnosis. On the basis of their morphology, we propose that they be classified as feline ductal adenoma/carcinoma and feline intraductal papillary adenoma/carcinoma, respectively. They overlap with their canine counterparts and lack the typical myoepithelial differentiation patterns seen in canine complex neoplasms, and therefore, the term complex should be avoided in felines. This study will add new information on FMT classification and be useful for prognostic studies.

  17. Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.

    Science.gov (United States)

    Liu, Xin; Pitarresi, Jason R; Cuitiño, Maria C; Kladney, Raleigh D; Woelke, Sarah A; Sizemore, Gina M; Nayak, Sunayana G; Egriboz, Onur; Schweickert, Patrick G; Yu, Lianbo; Trela, Stefan; Schilling, Daniel J; Halloran, Shannon K; Li, Maokun; Dutta, Shourik; Fernandez, Soledad A; Rosol, Thomas J; Lesinski, Gregory B; Shakya, Reena; Ludwig, Thomas; Konieczny, Stephen F; Leone, Gustavo; Wu, Jinghai; Ostrowski, Michael C

    2016-09-01

    The contribution of the microenvironment to pancreatic acinar-to-ductal metaplasia (ADM), a preneoplastic transition in oncogenic Kras-driven pancreatic cancer progression, is currently unclear. Here we show that disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a Kras(G12D) mouse model increased ADM. Smo-deleted fibroblasts had higher expression of transforming growth factor-α (Tgfa) mRNA and secreted higher levels of TGFα, leading to activation of EGFR signaling in acinar cells and increased ADM. The mechanism involved activation of AKT and noncanonical activation of the GLI family transcription factor GLI2. GLI2 was phosphorylated at Ser230 in an AKT-dependent fashion and directly regulated Tgfa expression in fibroblasts lacking Smo Additionally, Smo-deleted fibroblasts stimulated the growth of Kras(G12D)/Tp53(R172H) pancreatic tumor cells in vivo and in vitro. These results define a non-cell-autonomous mechanism modulating Kras(G12D)-driven ADM that is balanced by cross-talk between Hedgehog/SMO and AKT/GLI2 pathways in stromal fibroblasts. © 2016 Liu et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Basaloid ductal carcinoma in situ arising in salivary gland metaplasia of the breast: a case report.

    Science.gov (United States)

    Jang, Eun Jeong; Kang, Su Hwan; Bae, Young Kyung

    2014-01-01

    Salivary gland metaplasia is a newly recognized, adenosis-like lesion which could not be classified according to known categories of adenosis of the breast. We report a case of basaloid ductal carcinoma in situ (DCIS) arising in a background of salivary gland metaplasia in a 49-year old woman who visited our hospital for a right breast mass. Breast ultrasonography showed a multi-lobulating mixed hypoechoic and isoechoic mass measuring 2.9 cm in size at the periareolar area. Histologically, the lesion showed a well-defined DCIS with basaloid tumor cells and central comedo-type necrosis surrounded by salivary gland metaplasia composed of glands or ducts not specific to the breast, ducts with cribriform proliferation of luminal epithelial cells, and ducts with varying degrees of proliferation of basaloid cells including solid nests of basaloid cells. Salivary gland metaplasia is a most unusual lesion of the breast characterized by salivary gland-type acini and ducts with various proliferations of luminal and basaloid cells, and accompanied by malignant tumor of basal cell type.

  19. Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Hexige, Saiyin; Ardito-Abraham, Christine M; Wu, Yanhua; Wei, Youheng; Fang, Yuan; Han, Xu; Li, Jianang; Zhou, Ping; Yi, Qing; Maitra, Anirban; Liu, Jun O; Tuveson, David A; Lou, Wenhui; Yu, Long

    2015-06-01

    Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    Science.gov (United States)

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce; Gonzalez-Begne, Mireya; Halgand, Frédéric; Hall, Steven C.; Han, Xuemei; Henson, Bradley; Hewel, Johannes; Hu, Shen; Jeffrey, Sherry; Jiang, Jiang; Loo, Joseph A.; Ogorzalek Loo, Rachel R.; Malamud, Daniel; Melvin, James E.; Miroshnychenko, Olga; Navazesh, Mahvash; Niles, Richard; Park, Sung Kyu; Prakobphol, Akraporn; Ramachandran, Prasanna; Richert, Megan; Robinson, Sarah; Sondej, Melissa; Souda, Puneet; Sullivan, Mark A.; Takashima, Jona; Than, Shawn; Wang, Jianghua; Whitelegge, Julian P.; Witkowska, H. Ewa; Wolinsky, Lawrence; Xie, Yongming; Xu, Tao; Yu, Weixia; Ytterberg, Jimmy; Wong, David T.; Yates, John R.; Fisher, Susan J.

    2009-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes ranging from structural functions to enzymatic/catalytic activities. As expected, the majority mapped to the extracellular and secretory compartments. An immunoblot approach was used to validate the presence in saliva of a subset of the proteins identified by mass spectrometric approaches. These experiments focused on novel constituents and proteins for which the peptide evidence was relatively weak. Ultimately, information derived from the work reported here and related published studies can be used to translate blood-based clinical laboratory tests into a format that utilizes saliva. Additionally, a catalogue of the salivary proteome of healthy individuals allows future analyses of salivary samples from individuals with oral and systemic diseases, with the goal of identifying biomarkers with diagnostic and/or prognostic value for these conditions; another possibility is the discovery of therapeutic targets. PMID:18361515

  1. Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis.

    Science.gov (United States)

    Chishiki, Mayuko; Takagi, Kiyoshi; Sato, Ai; Miki, Yasuhiro; Yamamoto, Yuta; Ebata, Akiko; Shibahara, Yukiko; Watanabe, Mika; Ishida, Takanori; Sasano, Hironobu; Suzuki, Takashi

    2017-07-01

    It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ (DCIS) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 status was significantly associated with tumor size, nuclear grade, comedo necrosis, van Nuys classification, and Ki-67 labeling index. Subsequent in vitro studies indicated that CYC1 was significantly associated with mitochondrial membrane potential in MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. 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 KrasG12D 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.

  3. Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection.

    Science.gov (United States)

    Drifka, Cole R; Loeffler, Agnes G; Mathewson, Kara; Keikhosravi, Adib; Eickhoff, Jens C; Liu, Yuming; Weber, Sharon M; Kao, W John; Eliceiri, Kevin W

    2016-11-15

    Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value. We hypothesized that the alignment of collagen is associated with PDAC patient survival. To address this, pathology-confirmed tissues from 114 PDAC patients that underwent curative-intent surgery were retrospectively imaged with Second Harmonic Generation (SHG) microscopy, quantified with fiber segmentation algorithms, and correlated to patient survival. The same tissue regions were analyzed for epithelial-to-mesenchymal (EMT), α-SMA, and syndecan-1 using complimentary immunohistostaining and visualization techniques. Significant inter-tumoral variation in collagen alignment was found, and notably high collagen alignment was observed in 12% of the patient cohort. Stratification of patients according to collagen alignment revealed that high alignment is an independent negative factor following PDAC resection (p = 0.0153, multivariate). We also found that epithelial expression of EMT and the stromal expression of α-SMA and syndecan-1 were positively correlated with collagen alignment. In summary, stromal collagen alignment may provide additional, clinically-relevant information about PDAC tumors and underscores the importance of stroma-cancer interactions.

  4. Correlation between imaging and pathology in ductal carcinoma in situ of the breast

    Directory of Open Access Journals (Sweden)

    de Vries Jaap

    2004-03-01

    Full Text Available Abstract Background It is helpful in planning treatment for patients with ductal carcinoma in situ (DCIS if the size and grade could be reliably predicted from the mammography. The aims of this study were to determine if the type of calcification can be best used to predict histopathological grade from the mammograms, to examine the association of mammographic appearance of DCIS with grade and to assess the correlation between mammographic size and pathological size. Methods Mammographic films and pathological slides of 115 patients treated for DCIS between 1986 and 2000 were reviewed and reclassified by a single radiologist and a single pathologist respectively. Prediction models for the European Pathologist Working Group (EPWG and Van Nuys classifications were generated by ordinal regression. The association between mammographic appearance and grade was tested with the χ2-test. Relation of mammographic size with pathological size was established using linear regression. The relation was expressed by the correlation coefficient (r. Results The EPWG classification was correctly predicted in 68%, and the Van Nuys classification in 70% if DCIS was presented as microcalcifications. High grade was associated with presence of linear calcifications (p Conclusions Prediction of histopathological grade of DCIS presenting as microcalcifications is comparable using the Van Nuys and EPWG classification. There is no strict association of mammographic appearance with histopathological grade. There is a better linear relation between mammographic- and pathological size of DCIS presented as microcalcifications than as a density, although both relations are statistically significant.

  5. High expression of WISP-1 correlates with poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Yang, Jian-Yu; Yang, Min-Wei; Huo, Yan-Miao; Liu, Wei; Liu, De-Jun; Li, Jiao; Zhang, Jun-Feng; Hua, Rong; Sun, Yong-Wei

    2015-01-01

    WNT1 inducible signaling pathway protein 1 (WISP-1) is a member of the CCN family of growth factors and reported to possess an important role in tumorigenesis by triggering downstream events via integrin signaling. However, the exact role of WISP-1 in cancer remains unclear. In this study, we examined the expression pattern of WISP-1 at both mRNA and protein levels and evaluated the prognostic value of WISP-1 in pancreatic ductal adenocarcinoma (PDA). Expression of WISP-1 at mRNA level was upregulated in 17/24 tumor tissues compared to the matched adjacent non-tumor tissues and the result was confirmed by western blotting at protein level. Immunohistochemical staining of 194 pairs of PDA specimens suggested that high expression of WISP-1 is strongly correlated with clinical stage (P=0.003), T classification (P=0.008) and liver metastasis (P=0.012). Consistently, Kaplan-Meier survival curves indicated that patients with high expression of WISP-1 had a shorter survival time independent of clinical stage and lymphatic metastasis status. Moreover, univariate and multivariate analysis confirmed WISP-1 expression, age, classification and liver metastasis as independent prognostic factors for overall survival of PDA patients. Taken together, these results suggest that WISP-1 may serve as a potential prognostic biomarker for PDA.

  6. Treatment outcome of ductal carcinoma in situ patients treated with postoperative radiation therapy

    Science.gov (United States)

    Lim, Yu Jin; Chie, Eui Kyu; Han, Wonshik; Noh, Dong Young; Ha, Sung W.

    2014-01-01

    Purpose To evaluate the outcome of ductal carcinoma in situ (DCIS) patients who underwent surgery followed by radiation therapy (RT). Materials and Methods We retrospectively reviewed 106 DCIS patients who underwent surgery followed by postoperative RT between 1994 and 2006. Ninety-four patients underwent breast-conserving surgery, and mastectomy was performed in 12 patients due to extensive DCIS. Postoperative RT was delivered to whole breast with 50.4 Gy/28 fx. Tumor bed boost was offered to 7 patients (6.6%). Patients with hormonal receptor-positive tumors were treated with hormonal therapy. Results The median follow-up duration was 83.4 months (range, 33.4 to 191.5 months) and the median age was 47.8 years. Ten patients (9.4%) had resection margin <1 mm and high-grade and estrogen receptor-negative tumors were observed in 39 (36.8%) and 20 (18.9%) patients, respectively. The 7-year ipsilateral breast tumor recurrence (IBTR)-free survival rate was 95.3%. Resection margin (<1 or ≥1 mm) was the significant prognostic factor for IBTR in univariate and multivariate analyses (p < 0.001 and p = 0.016, respectively). Conclusion Postoperative RT for DCIS can achieve favorable treatment outcome. Resection margin was the important prognostic factor for IBTR in the DCIS patients who underwent postoperative RT. PMID:24724045

  7. The Problems of Radiofrequency Ablation as an Approach for Advanced Unresectable Ductal Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2010-07-01

    Full Text Available Advanced ductal pancreatic carcinoma (PC remains a challenge for current surgical and medical approaches. It has recently been claimed that radiofrequency ablation (RFA may be beneficial for patients with locally advanced or metastatic PC. Using the MEDLINE database, we found seven studies involving 106 patients in which PC was treated using RFA. The PC was mainly located in the pancreatic head (66.9% with a median size of 4.6 cm. RFA was carried out in 85 patients (80.1% with locally advanced PC and in 21 (19.9% with metastatic disease. Palliative surgical procedures were carried out in 41.5% of the patients. The average temperature used was 90 °C (with a temperature range of 30–105 °C and the ratio between the number of passes of the probe and the size of the tumor in centimeters was 0.5 (range of 0.36–1. The median postoperative morbidity and mortality were 28.3% and 7.5%, respectively; the median survival was 6.5 months (range of 1–33 months. In conclusion, RFA is a feasible technique: however, its safety and long-term results are disappointing; Thus, the RFA procedure should not be recommended in clinical practice for a PC patient.

  8. 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.

  9. Ballistic penetration test results for Ductal and ultra-high performance concrete samples.

    Energy Technology Data Exchange (ETDEWEB)

    Reinhart, William Dodd; Thornhill, Tom Finley, III (KTech)

    2010-03-01

    This document provides detailed test results of ballistic impact experiments performed on several types of high performance concrete. These tests were performed at the Sandia National Laboratories Shock Thermodynamic Applied Research Facility using a 50 caliber powder gun to study penetration resistance of concrete samples. This document provides test results for ballistic impact experiments performed on two types of concrete samples, (1) Ductal{reg_sign} concrete is a fiber reinforced high performance concrete patented by Lafarge Group and (2) ultra-high performance concrete (UHPC) produced in-house by DoD. These tests were performed as part of a research demonstration project overseen by USACE and ERDC, at the Sandia National Laboratories Shock Thermodynamic Applied Research (STAR) facility. Ballistic penetration tests were performed on a single stage research powder gun of 50 caliber bore using a full metal jacket M33 ball projectile with a nominal velocity of 914 m/s (3000 ft/s). Testing was observed by Beverly DiPaolo from ERDC-GSL. In all, 31 tests were performed to achieve the test objectives which were: (1) recovery of concrete test specimens for post mortem analysis and characterization at outside labs, (2) measurement of projectile impact velocity and post-penetration residual velocity from electronic and radiographic techniques and, (3) high-speed photography of the projectile prior to impact, impact and exit of the rear surface of the concrete construct, and (4) summarize the results.

  10. 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.

  11. A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Anna S. Gerdtsson

    2015-01-01

    Full Text Available Background. Pancreatic ductal adenocarcinoma (PDAC is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD and controls with nonpancreatic conditions (NPC, was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i sampling from five different hospitals could not be identified as a preanalytical variable and (ii a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91–100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.

  12. 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.

  13. Invasive micropapillary carcinoma of the breast: MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyo Soon; Jeong, Seo In; Choi, You Ri; Kim, Jin Woong; Lee, Ji Shin; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Kuzmiak, Cherie M. [Department of Radiology, University of North Carolina, Chapel Hill (Korea, Republic of)

    2013-08-15

    To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast. MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied. The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%). Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.

  14. Ecology of forest insect invasions

    Science.gov (United States)

    E.G. Brockerhoff; A.M. Liebhold

    2017-01-01

    Forests in virtually all regions of the world are being affected by invasions of non-native insects. We conducted an in-depth review of the traits of successful invasive forest insects and the ecological processes involved in insect invasions across the universal invasion phases (transport and arrival, establishment, spread and impacts). Most forest insect invasions...

  15. Cdk4 regulates recruitment of quiescent beta-cells and ductal epithelial progenitors to reconstitute beta-cell mass.

    Directory of Open Access Journals (Sweden)

    Ji-Hyeon Lee

    2010-01-01

    Full Text Available Insulin-producing pancreatic islet beta cells (beta-cells are destroyed, severely depleted or functionally impaired in diabetes. Therefore, replacing functional beta-cell mass would advance clinical diabetes management. We have previously demonstrated the importance of Cdk4 in regulating beta-cell mass. Cdk4-deficient mice display beta-cell hypoplasia and develop diabetes, whereas beta-cell hyperplasia is observed in mice expressing an active Cdk4R24C kinase. While beta-cell replication appears to be the primary mechanism responsible for beta-cell mass increase, considerable evidence also supports a contribution from the pancreatic ductal epithelium in generation of new beta-cells. Further, while it is believed that majority of beta-cells are in a state of 'dormancy', it is unclear if and to what extent the quiescent cells can be coaxed to participate in the beta-cell regenerative response. Here, we address these queries using a model of partial pancreatectomy (PX in Cdk4 mutant mice. To investigate the kinetics of the regeneration process precisely, we performed DNA analog-based lineage-tracing studies followed by mathematical modeling. Within a week after PX, we observed considerable proliferation of islet beta-cells and ductal epithelial cells. Interestingly, the mathematical model showed that recruitment of quiescent cells into the active cell cycle promotes beta-cell mass reconstitution in the Cdk4R24C pancreas. Moreover, within 24-48 hours post-PX, ductal epithelial cells expressing the transcription factor Pdx-1 dramatically increased. We also detected insulin-positive cells in the ductal epithelium along with a significant increase of islet-like cell clusters in the Cdk4R24C pancreas. We conclude that Cdk4 not only promotes beta-cell replication, but also facilitates the activation of beta-cell progenitors in the ductal epithelium. In addition, we show that Cdk4 controls beta-cell mass by recruiting quiescent cells to enter the cell

  16. 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.

  17. Minimally invasive lumbar fusion.

    Science.gov (United States)

    Foley, Kevin T; Holly, Langston T; Schwender, James D

    2003-08-01

    Review article. To provide an overview of current techniques for minimally invasive lumbar fusion. Minimally invasive techniques have revolutionized the management of pathologic conditions in various surgical disciplines. Although these same principles have been used in the treatment of lumbar disc disease for many years, minimally invasive lumbar fusion procedures have only recently been developed. The goals of these procedures are to reduce the approach-related morbidity associated with traditional lumbar fusion, yet allow the surgery to be performed in an effective and safe manner. The authors' clinical experience with minimally invasive lumbar fusion was reviewed, and the pertinent literature was surveyed. Minimally invasive approaches have been developed for common lumbar procedures such as anterior and posterior interbody fusion, posterolateral onlay fusion, and internal fixation. As with all new surgical techniques, minimally invasive lumbar fusion has a learning curve. As well, there are benefits and disadvantages associated with each technique. However, because these techniques are new and evolving, evidence to support their potential benefits is largely anecdotal. Additionally, there are few long-term studies to document clinical outcomes. Preliminary clinical results suggest that minimally invasive lumbar fusion will have a beneficial impact on the care of patients with spinal disorders. Outcome studies with long-term follow-up will be necessary to validate its success and allow minimally invasive lumbar fusion to become more widely accepted.

  18. 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 Impact factor: 4.900, year: 2016

  19. 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, Kristen; 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.

    2015-01-01

    Summary 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. PMID:26451490

  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. Omeprazole Inhibits Pancreatic Cancer Cell Invasion through a Nongenomic Aryl Hydrocarbon Receptor Pathway.

    Science.gov (United States)

    Jin, Un-Ho; Kim, Sang-Bae; Safe, Stephen

    2015-05-18

    Omeprazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are aryl hydrocarbon receptor (AhR) agonists that inhibit the invasion of breast cancer cells through inhibition of CXCR4 transcription. Treatment of highly invasive Panc1 pancreatic cancer cells with TCDD, omeprazole, and seven other AhR-active pharmaceuticals showed that only omeprazole and tranilast, but not TCDD, inhibited invasion in a Boyden chamber assay. Similar results were observed in MiaPaCa2 cells, another quasimensenchymal pancreatic ductal adenocarcinoma (QM-PDA) pancreatic cancer cell line, whereas invasion was not observed with BxPC3 or L3.6pL cells, which are classified as classical (less invasive) pancreatic cancer cells. It was also observed in QM-PDA cells that TCDD, omeprazole, and tranilast did not induce CYP1A1 or CXCR4 and that treatment with these compounds did not result in nuclear uptake of AhR. In contrast, treatment of BxPC3 and L3.6pL cells with these AhR ligands resulted in induction of CYP1A1 (by TCDD) and nuclear uptake of AhR, which was similar to that observed for Ah-responsive MDA-MB-468 breast and HepG2 liver cancer cell lines. Results of AhR and AhR nuclear translocator (Arnt) knockdown experiments in Panc1 and MiaPaCa2 cells demonstrated that omeprazole- and tranilast-mediated inhibition of invasion was AhR-dependent but Arnt-independent. These results demonstrate that in the most highly invasive subtype of pancreatic cancer cells (QM-PDA) the selective AhR modulators omeprazole and tranilast inhibit invasion through a nongenomic AhR pathway.

  2. Loss of heterozygosity at the BRCA1 and BRCA2 loci detected in ductal lavage fluid from BRCA gene mutation carriers and controls.

    Science.gov (United States)

    Locke, Imogen; Kote-Jarai, Zsofia; Bancroft, Elizabeth; Bullock, Sarah; Jugurnauth, Sarah; Osin, Peter; Nerurkar, Ashutosh; Izatt, Louise; Pichert, Gabriella; Gui, Gerald P H; Eeles, Rosalind A

    2006-07-01

    Female BRCA gene mutation carriers are at increased risk for developing breast cancer. Ductal lavage is a novel method for sampling breast ductal fluid, providing epithelial cells for cytologic assessment and a source of free DNA for molecular analyses. Loss of heterozygosity (LOH) at the BRCA loci in ductal lavage fluid is a potential biomarker of breast cancer risk. The LOH rate was measured at the BRCA1/2 loci and compared with that at a control locus (APC) using free DNA from the ductal lavage fluid of BRCA carriers and predictive test negative controls. We evaluated the reproducibility of these analyses. Free DNA sufficient for PCR amplification was obtained from 33 ductal lavage samples of 17 healthy women of known BRCA status (14 BRCA carriers and 3 controls). LOH rates of 36.4% to 56.3% at the BRCA1 locus and 45% to 61.5% at the BRCA2 locus were found among BRCA carriers. The LOH rate at the APC locus was lower (18.5%). The interaliquot reproducibility for the D17S855 marker of the BRCA1 locus was 66.7%. Intraaliquot reproducibility was 90%. Although we successfully isolated sufficient free DNA from ductal lavage fluid for PCR amplification, the degree of reproducibility of these LOH studies raises questions about the robustness of this technique as a risk assessment tool in the evaluation of high-risk women. Further studies are required to evaluate the specificity and predictive value of LOH in ductal lavage fluid for breast cancer development.

  3. 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

  4. 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.

  5. 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.

  6. Prostatic ductal adenocarcinoma: an aggressive tumour variant unrecognized on T2 weighted magnetic resonance imaging (MRI)

    Energy Technology Data Exchange (ETDEWEB)

    Schieda, Nicola; Coffey, Niamh; Al-Dandan, Omran; Shabana, Wael [The University of Ottawa, Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario (Canada); Gulavita, Previn; Flood, Trevor A. [The University of Ottawa, Department of Anatomical Pathology, The Ottawa Hospital, Ottawa (Canada)

    2014-06-15

    Prostatic ductal adenocarcinoma (DCa) is an aggressive variant. The purpose of this study was to determine if T2 signal intensity (SI) differs from conventional adenocarcinoma (CCa). A retrospective study of patients who underwent preoperative MRI and prostatectomy between 2009 and 2012 was performed. T2 SI ratios (SIR) for tumour (T) to obturator internus muscle (M) and normal peripheral zone (PZ) were compared. Two radiologists evaluated the central gland/PZ to detect tumours and compared diagnostic accuracy. T2 SIR for DCa were 3.60 (T/M), 0.66 (T/PZ); 2.68 (T/M), 0.47 (T/PZ) for Gleason 9; 2.50 (T/M), 0.47 (T/PZ) for Gleason 7/8 and 3.95 (T/M), 0.73 (T/PZ) for Gleason 6 tumours. There was a difference in T2 T/M and T/PZ SIR between DCa and Gleason 9 (p = 0.003, p = 0.004) and Gleason 7/8 (p = 0.006, p = 0.002), but no difference in SIR between DCa and Gleason 6 tumours. The sensitivity for tumour detection was 0-27 % for DCa, 64-82 % for Gleason 9, 44-88 % for Gleason 7-8 and 0-20 % for Gleason 6. There was a difference in the sensitivity of detecting Gleason 9 and 7/8 tumours when compared to DCa (p = 0.004, p = 0.001). DCa resembles Gleason score 6 tumour at T2-weighted MRI, which underestimates tumour grade and renders the tumour occult. (orig.)

  7. CDDO-Me inhibits tumor growth and prevents recurrence of pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Gao, Xiaohua; Deeb, Dorrah; Liu, Yongbo; Liu, Patricia; Zhang, Yiguan; Shaw, Jiajiu; Gautam, Subhash C

    2015-12-01

    Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) has shown potent antitumorigenic activity against a wide range of cancer cell lines in vitro and inhibited the growth of liver, lung and prostate cancer in vivo. In the present study, we examined the antitumor activity of CDDO-Me for pancreatic ductal adenocarcinoma (PDAC) cells with and without activating K-ras mutations. Treatment of K-ras mutant MiaPaCa-2 and K-ras normal BxPC-3 cells with CDDO-Me elicited strong antiproliferative and proapoptopic responses in both cell lines in culture. The inhibition of cell proliferation and induction of apoptosis was accompanied by the inhibition of antiapoptotic/prosurvival p-Akt, NF-кB and p-mTOR signaling proteins. For testing efficacy of CDDO-Me in vivo heterotopic and orthotopic xenografts were generated by implanting BxPC-3 and MiaPaCa-2 cells subcutaneously and in the pancreatic tail, respectively. Treatment with CDDO-Me significantly inhibited the growth of BxPC-3 xenografts and reduced the levels of p-Akt and p-mTOR in tumor tissue. In mice with orthotopic MiaPaCa-2 xenografts, treatment with CDDO-Me prolonged the survival of mice when administered following the surgical resection of tumors. The latter was attributed to the eradication of residual PDAC remaining after resection of tumors. These preclinical data demonstrate the potential of CDDO-Me for treating primary PDAC tumors and for preventing relapse/recurrence through the destruction of residual disease.

  8. Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene.

    Science.gov (United States)

    Schmohl, Kathrin A; Gupta, Aayush; Grünwald, Geoffrey K; Trajkovic-Arsic, Marija; Klutz, Kathrin; Braren, Rickmer; Schwaiger, Markus; Nelson, Peter J; Ogris, Manfred; Wagner, Ernst; Siveke, Jens T; Spitzweg, Christine

    2017-05-16

    The theranostic sodium iodide symporter (NIS) gene allows detailed molecular imaging of transgene expression and application of therapeutic radionuclides. As a crucial step towards clinical application, we investigated tumor specificity and transfection efficiency of epidermal growth factor receptor (EGFR)-targeted polyplexes as systemic NIS gene delivery vehicles in an advanced genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) that closely reflects human disease. PDAC was induced in mice by pancreas-specific activation of constitutively active KrasG12D and deletion of Trp53. We used tumor-targeted polyplexes (LPEI-PEG-GE11/NIS) based on linear polyethylenimine, shielded by polyethylene glycol and coupled with the EGFR-specific peptide ligand GE11, to target a NIS-expressing plasmid to high EGFR-expressing PDAC. In vitro iodide uptake studies in cell explants from murine EGFR-positive and EGFR-ablated PDAC lesions demonstrated high transfection efficiency and EGFR-specificity of LPEI-PEG-GE11/NIS. In vivo 123I gamma camera imaging and three-dimensional high-resolution 124I PET showed significant tumor-specific accumulation of radioiodide after systemic LPEI-PEG-GE11/NIS injection. Administration of 131I in LPEI-PEG-GE11/NIS-treated mice resulted in significantly reduced tumor growth compared to controls as determined by magnetic resonance imaging, though survival was not significantly prolonged. This study opens the exciting prospect of NIS-mediated radionuclide imaging and therapy of PDAC after systemic non-viral NIS gene delivery.

  9. Does Second Reader Opinion Affect Patient Management in Pancreatic Ductal Adenocarcinoma?

    Science.gov (United States)

    Corrias, Giuseppe; Huicochea Castellanos, Sandra; Merkow, Ryan; Langan, Russel; Balachandran, Vinod; Ragucci, Monica; Carollo, Gabriella; Mancini, Marcello; Saba, Luca; Mannelli, Lorenzo

    2018-01-16

    To determine the impact of second-opinion assessment on cancer staging and patient management in patients with pancreatic ductal adenocarcinoma. This retrospective study was approved by our institutional review board with a waiver of informed consent. Second-opinion reports between January 1, 2009 and December 31, 2013, alongside outside reports for 65 consecutive cases of biopsy-proven pancreatic adenocarcinomas, were presented in random order to two experienced abdominal surgeons who independently reviewed them blinded to the origin of the report, images of the examinations, and patient identifier. Each surgeon filled in a questionnaire for each report recommending cancer staging and patient management. Recommended patient management and staging were evaluated against reference standards (actual patient management at 6 months following second-opinion assessment, and pathology or other clinical and imaging reference standards at 6 months or longer, respectively) using Cohen kappa. Cancer staging differed in 13% (9 of 65) of cases for surgeon 1 and in 18.4% (12 of 65) for surgeon 2. Patient management changed in 38.4% (25 of 65) of cases for surgeon 1 and in 20% (13 of 65) for surgeon 2. When compared to the pathologic staging gold standard, second opinion was correct in 85.7% (six of seven) of the time for both surgeons. Recommended patient management from second-opinion reports showed good agreement with the reference standard (weighted k = 0.6467 [0.4014-0.892] and weighted k = 0.6262 [0.3954-0.857] for surgeon 2). Second-opinion review by subspecialized oncologic radiologists can impact patient care, specifically in terms of management decision. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  10. Value of pre-operative breast MRI for the size assessment of ductal carcinoma in situ

    Science.gov (United States)

    Proulx, Francesca; Correa, José A; Ferré, Romuald; Omeroglu, Atilla; Aldis, Ann; Meterissian, Sarkis

    2016-01-01

    Objective: To retrospectively evaluate the accuracy of pre-operative breast MRI and mammography in determining the size of ductal carcinoma in situ (DCIS) compared with the histopathological results. Methods: 79 patients [mean age: 56.5 (standard deviation 10.2) years] with pathologically proven DCIS (79 lesions) obtained a bilateral mammogram and a pre-operative contrast-enhanced MRI. The accuracy of MRI and mammography to detect tumour size were estimated and compared, using histopathological size as the gold standard, on the subjects with measurements with both modalities (n = 60). Results: MRI detected 67 (85%) lesions, mammography detected 72 (91%) and both modalities detected 60 (76%). Median DCIS size detected by mammography vs MRI was smaller (1.55 vs 1.65 cm). Out of these 60 cases, compared with the histopathological size, the accuracy of MRI and mammography was 0.66 and 0.56, respectively (p = 0.045). MRI showed better accuracy than mammography for younger patients (age ≤ 50 years, p = 0.003). For tumour nuclear grade, there was a statistically significant difference for the intermediate level, with higher accuracy for MRI (p = 0.03). Conclusion: MRI was more accurate than mammography in DCIS size assessment when visible, particularly in lesions of intermediate grade and in patients less than 50 years of age. Advances in knowledge: Breast MRI may help in management of DCIS of intermediate grade and in females less than 50 years of age. PMID:26568438

  11. 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.

  12. Mammographic bi-dimensional product: a powerful predictor of successful excision of ductal carcinoma in situ

    Energy Technology Data Exchange (ETDEWEB)

    Evans, A. [Breast Institute, Nottingham City Hospital, Nottingham (United Kingdom)]. E-mail: andrew.evans@nuh.nhs.uk; Clements, K. [West Midlands Cancer Intelligence Unit, Birmingham (United Kingdom); Maxwell, A. [Bolton Breast Unit, Bolton (United Kingdom); Dobson, H. [West of Scotland Breast Screening Unit, Glasgow (United Kingdom); Wallis, M. [Warwickshire, Solihull and Coventry Breast Screening Service, Coventry (United Kingdom); Lawrence, G. [West Midlands Cancer Intelligence Unit, Birmingham (United Kingdom); Bishop, H. [Bolton Breast Unit, Bolton (United Kingdom)

    2007-08-15

    Background: The aim of this analysis was to ascertain whether uni-dimensional measurement of mammographic microcalcification, the product of bi-dimensional measurement, calcification morphology, and pathological grade are helpful in predicting successful single therapeutic wide local excision (WLE) of ductal carcinoma in situ (DCIS). Methods: The study group comprised 505 patients whose mammograms showed the DCIS as calcification, and in whom a non-operative diagnosis had been obtained and WLE attempted. The extents of mammographic calcifications was measured in two planes at 90{sup o} on the oblique view, the appearances classified as comedo, granular, or punctate. DCIS was graded using cyto-nuclear characteristics. Results: Three hundred and forty-two patients had a successful first WLE and 163 patients had further surgery. A uni-dimensional measurement of <35 mm and a bi-dimensional product of <800 mm{sup 2} were associated with successful excision (69 versus 54%, p = 0.02 and 70 versus 27%, p = 0.0001, respectively). Mammographic calcification morphology and histological grade did not influence the likelihood of a successful first WLE. For high-grade DCIS, the upper limit of the bi-dimensional product associated with successful WLE was 800 mm{sup 2} (69 versus 24%, p = 0.0003). In contrast, for non-high-grade DCIS, the cut-off was 400 mm{sup 2} (73 versus 33%, p = 0.01). Analyses based on mammographic calcification morphology gave similar findings. Conclusion: The mammographic bi-dimensional product is a powerful predictor of successful WLE of DCIS when combined with histological grade and/or calcification morphology.

  13. Association of increased DNA methyltransferase expression with carcinogenesis and poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhang, Jing-Jing; Zhu, Yi; Zhu, Yan; Wu, Jun-Li; Liang, Wen-Biao; Zhu, Rong; Xu, Ze-Kuan; Du, Qing; Miao, Yi

    2012-02-01

    Epigenetic modifications play an important role in multistage carcinogenesis. The role of the three functional DNA methyltransferases (DNMTs) in pancreatic carcinogenesis has not been fully understood. The main goal of this study was to examine DNMT expression in different stages of pancreatic ductal adenocarcinoma (PDAC), and evaluate their prognostic significance in PDAC. A large number of premalignant and malignant pancreatic lesions were obtained by manual microdissection. Quantitative real-time RT-PCR was used to detect DNMTs mRNA expression. Nonparametric test, logrank test and Cox regression analysis were used to evaluate the clinical significance of DNMT expression. The mRNA expression of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC, and were statistically correlated with each other. Expression of the three DNMTs was statistically correlated with TNM staging and history of chronic pancreatitis. DNMT3A and DNMT3B, but not DNMT1 expression, was statistically correlated with tumour size. Patients with higher levels of DNMT1, DNMT3A and/or DNMT3B expression had an overall lower survival than those with lower levels of expression. Univariate analysis showed that high expression levels of DNMTs, alcohol consumption, tumour differentiation and TNM staging were statistically significant risk factors. Multivariate analysis showed that high level of DNMT3B expression and tumour differentiation were statistically significant independent poor prognostic factors. These results suggested that pancreatic carcinogenesis involves an increased mRNA expression of three DNMTs, and they may become valuable diagnostic and prognostic markers as well as potential therapeutic targets for pancreatic cancer.

  14. 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.

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

    Science.gov (United States)

    Ponti, Antonio; Lynge, Elsebeth; James, Ted; Májek, Ondřej; von Euler-Chelpin, My; Anttila, Ahti; Fitzpatrick, Patricia; Mano, Maria Piera; Kawai, Masaaki; Scharpantgen, Astrid; Fracheboud, Jacques; Hofvind, Solveig; Vidal, Carmen; Ascunce, Nieves; Salas, Dolores; Bulliard, Jean-Luc; Segnan, Nereo; Kerlikowske, Karla; Taplin, Stephen

    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 evaluate the potential for treatment related morbidity. Methods We sought screen-detected DCIS data from the ICSN countries identified during 2004–2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. Results Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50–69 years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67–90% of DCIS received breast conservation surgery (BCS), and in 41–100% of the cases this was followed by radiotherapy; 6.4–59% received sentinel lymph node biopsy (SLNB) only and 0.8–49% axillary dissection (ALND) with 0.6% (range by programmes 0–8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. Conclusions Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction. PMID:25149183

  16. Ductal Carcinoma in Situ-The Influence of the Radiotherapy Boost on Local Control

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Philip [Division of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Lambert, Christine, E-mail: christine.lambert@muhc.mcgill.ca [Division of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Agnihotram, Ramanakumar V. [Division of Cancer Epidemiology, Department of Oncology, McGill University, Montreal, QC (Canada); David, Marc; Duclos, Marie; Freeman, Carolyn R. [Division of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada)

    2012-02-01

    Purpose: Local recurrence (LR) of ductal carcinoma in situ (DCIS) is reduced by whole-breast irradiation after breast-conserving surgery (BCS). However, the benefit of adding a radiotherapy boost to the surgical cavity for DCIS is unclear. We sought to determine the impact of the boost on LR in patients with DCIS treated at the McGill University Health Centre. Methods and Materials: A total of 220 consecutive cases of DCIS treated with BCS and radiotherapy between January 2000 and December 2006 were reviewed. Of the patients, 36% received a radiotherapy boost to the surgical cavity. Median follow-up was 46 months for the boost and no-boost groups. Kaplan-Meier survival analyses and Cox regression analyses were performed. Results: Compared with the no-boost group, patients in the boost group more frequently had positive and <0.1-cm margins (48% vs. 8%) (p < 0.0001) and more frequently were in higher-risk categories as defined by the Van Nuys Prognostic (VNP) index (p = 0.006). Despite being at higher risk for LR, none (0/79) of the patients who received a boost experienced LR, whereas 8 of 141 patients who did not receive a boost experienced an in-breast LR (log-rank p = 0.03). Univariate analysis of prognostic factors (age, tumor size, margin status, histological grade, necrosis, and VNP risk category) revealed only the presence of necrosis to significantly correlate with LR (log-rank p = 0.003). The whole-breast irradiation dose and fractionation schedule did not affect LR rate. Conclusions: Our results suggest that the use of a radiotherapy boost improves local control in DCIS and may outweigh the poor prognostic effect of necrosis.

  17. Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

    Energy Technology Data Exchange (ETDEWEB)

    Shaitelman, Simona F.; Grills, Inga S.; Kestin, Larry L.; Ye Hong; Nandalur, Sirisha; Huang Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Vicini, Frank A., E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-12-01

    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.

  18. 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

    2017-11-22

    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

  19. 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 de