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Sample records for human ductal breast

  1. High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast.

    Science.gov (United States)

    Somiari, Richard I; Sullivan, Anthony; Russell, Stephen; Somiari, Stella; Hu, Hai; Jordan, Rick; George, Alisha; Katenhusen, Richard; Buchowiecka, Alicja; Arciero, Cletus; Brzeski, Henry; Hooke, Jeff; Shriver, Craig

    2003-10-01

    Large-scale proteomics will play a critical role in the rapid display, identification and validation of new protein targets, and elucidation of the underlying molecular events that are associated with disease development, progression and severity. However, because the proteome of most organisms are significantly more complex than the genome, the comprehensive analysis of protein expression changes will require an analytical effort beyond the capacity of standard laboratory equipment. We describe the first high-throughput proteomic analysis of human breast infiltrating ductal carcinoma (IDCA) using OCT (optimal cutting temperature) embedded biopsies, two-dimensional difference gel electrophoresis (2-D DIGE) technology and a fully automated spot handling workstation. Total proteins from four breast IDCAs (Stage I, IIA, IIB and IIIA) were individually compared to protein from non-neoplastic tissue obtained from a female donor with no personal or family history of breast cancer. We detected differences in protein abundance that ranged from 14.8% in stage I IDCA versus normal, to 30.6% in stage IIB IDCA versus normal. A total of 524 proteins that showed > or = three-fold difference in abundance between IDCA and normal tissue were picked, processed and identified by mass spectrometry. Out of the proteins picked, approximately 80% were unambiguously assigned identities by matrix-assisted laser desorbtion/ionization-time of flight mass spectrometry or liquid chromatography-tandem mass spectrometry in the first pass. Bioinformatics tools were also used to mine databases to determine if the identified proteins are involved in important pathways and/or interact with other proteins. Gelsolin, vinculin, lumican, alpha-1-antitrypsin, heat shock protein-60, cytokeratin-18, transferrin, enolase-1 and beta-actin, showed differential abundance between IDCA and normal tissue, but the trend was not consistent in all samples. Out of the proteins with database hits, only heat shock

  2. Breast ductal endoscopy: how many procedures qualify?

    Directory of Open Access Journals (Sweden)

    Papalabros Alexandros

    2009-06-01

    Full Text Available Abstract Background Breast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training beyond which ductal endoscopy is successfully performed. Findings Ten breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier. Conclusion These pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable.

  3. Breast ductal endoscopy: how many procedures qualify?

    Science.gov (United States)

    Zagouri, Flora; Sergentanis, Theodoros N; Giannakopoulou, Georgia; Panopoulou, Effrosyni; Chrysikos, Dimosthenis; Bletsa, Garifallia; Flessas, John; Filippakis, George; Papalabros, Alexandros; Bramis, Kostas J; Zografos, George C

    2009-01-01

    Background Breast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training) beyond which ductal endoscopy is successfully performed. Findings Ten breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier. Conclusion These pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable. PMID:19566939

  4. Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.

    Science.gov (United States)

    Zumwalde, Nicholas A; Haag, Jill D; Sharma, Deepak; Mirrielees, Jennifer A; Wilke, Lee G; Gould, Michael N; Gumperz, Jenny E

    2016-04-01

    Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2(+) γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNγ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2(+) γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.

  5. Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma.

    Science.gov (United States)

    Martin, Tracey Amanda; Jiang, Wen Guo

    2014-01-01

    The tumor stem cell theory could explain how patients with metastatic disease show clinical relapse several months after starting treatment due to the survival of a small group of cells with unique characteristics. We examined the distribution and expression of a panel of stem cell markers in human breast cancer primary tumors. Human breast tissues were processed for immunohistochemistry, and RNA was extracted for analysis by quantitative-PCR. Immunohistochemical assay revealed that CD44 was strongly expressed in background endothelia and epithelia. CD133 expression was lost in tumor-associated endothelial cells. Conversely, CD49b was strongly stained in the tumors, associated vessels and ducts but was weakly stained in the background epithelia. q-PCR analysis revealed that CD44 and PSCA were reduced in patients with poor outcome (metastatic disease and death from breast cancer), with a marked reduction in ductal carcinoma, particularly with metastasis to bone although these did not reach significant difference. CD133 was significantly reduced in patients with metastatic disease and was also significantly reduced in patients with ductal carcinoma/bone metastasis. Conversely, CD49F was increased in patients with a poor outcome and those with ductal cancer and bone metastases. This is the first study to determine the distribution and expression pattern of these stem cell markers in human breast cancer. There was a significant association between loss of expression and metastatic disease in patients with breast cancer. Such differential expression may play a part in breast cancer disease progression, and suggests that the current stem cell theory may not hold true for all cancer types.

  6. DUCTAL CARCINOMA IN SITU OF THE BREAST

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the clinical characteristics, treatment and prognosis of ductal carcinoma in situ (DCIS) of the breast. Methods: Clinicopathological and follow-up data were collected in 52 patients with DCIS. Results: The clinic data showed that 50 patients had signs of breast lumps or/and nipple discharges, 2 patients presented abnormal mammography; 2 patients had lymph node involved; and 14 patients were accompanied with intraductal papillomatosis. All patients were Received surgical therapy. The follow-up data showed 1 patient locally recurred after lumpectomy, and was underwent mastectomy again, then cured. There were no patients died of DCIS. Conclusion: Mastectomy should be a standard surgical mode, and the prognosis of DCIS was favorable, but mammography for screening of asymptomatic women should be strengthened to find DCIS.

  7. 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

  8. 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 susceptibilit

  9. Cyclooxygenase-2 and human epidermal growth factor receptor type 2 (HER-2 expression simultaneously in invasive and in situ breast ductal carcinoma

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    Adrienne Pratti Lucarelli

    Full Text Available CONTEXT AND OBJECTIVE: Cyclooxygenase-2 (COX-2 and human epidermal growth factor receptor type 2 (HER-2 are associated with tumorigenesis. Studies have shown that HER-2 can regulate COX-2 expression. The aim of this study was to evaluate the correlation between COX-2 and HER-2 expression in normal breast epithelium and in ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC present in the same breast. DESIGN AND SETTING: Cross-sectional study at the Mastology Unit of the Department of Gynecology and Obstetrics, Santa Casa de Misericórdia de São Paulo Hospital. METHODS: COX-2 and HER-2 were detected using immunohistochemistry on 100 tissue fragments. HER-2 > +2 was subjected to fluorescence in situ hybridization (FISH. RESULTS: COX-2 expression was detected in 87%, 85% and 75% of IDC, DCIS and normal epithelium, respectively. HER-2 expression was detected in 34% of IDC and 34% of DCIS. COX-2 in DCIS correlated with HER-2 in IDC (P = 0.049 and DCIS (P = 0.049. COX-2 in normal epithelium correlated with HER-2 in IDC (P = 0.046 and DCIS (P = 0.046. COX-2 in IDC was not associated with HER-2 (P = 0.235. Comparison between COX-2 and HER-2 in DCIS showed that there was a statistically significant difference with regard to nuclear grades II and III and presence of comedonecrosis (P < 0.001. In IDC, there was significant expression with nuclear grades II and III and histological grade II (P < 0.001. CONCLUSIONS: Our findings provide evidence that HER-2 and COX-2 regulate each other

  10. Ductal lavage, nipple aspiration, and ductoscopy for breast cancer diagnosis.

    Science.gov (United States)

    Dooley, William C

    2003-01-01

    The intraductal approach to breast cancer has been invigorated this year by a series of papers exploring ductal-based screening through nipple aspiration and lavage and ductal exploration through endoscopy. The merging of these efforts to define the earliest biologic changes in the progression toward breast cancer is opening new fields for both bench-translational and clinical research. These techniques have already begun to show value in defining the presence and extent of proliferative disease in high-risk patients, allowing for more informed therapeutic decision making.

  11. In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

    Science.gov (United States)

    Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetics is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structura...

  12. Invasive ductal breast cancer metastatic to the sigmoid colon

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    Zhou Xiao-cong

    2012-11-01

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

  13. RNA-Seq of Human Breast Ductal Carcinoma In Situ Models Reveals Aldehyde Dehydrogenase Isoform 5A1 as a Novel Potential Target

    Science.gov (United States)

    Kaur, Hitchintan; Mao, Shihong; Li, Quanwen; Sameni, Mansoureh; Krawetz, Stephen A.; Sloane, Bonnie F.; Mattingly, Raymond R.

    2012-01-01

    Breast ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. To increase knowledge of DCIS, we determined the expression changes that are common among three DCIS models (MCF10.DCIS, SUM102 and SUM225) compared to the MCF10A model of non-tumorigenic mammary epithelial cells in three dimensional (3D) overlay culture with reconstituted basement membrane (rBM). Extracted mRNA was subjected to 76 cycles of deep sequencing (RNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of RNA-Seq results showed 295 consistently differentially expressed transcripts in the DCIS models. These differentially expressed genes encode proteins that are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFβ signaling, show association with cell-cell signaling, cell-cell adhesion and cell proliferation, and have a notable bias toward localization in the extracellular and plasma membrane compartments. RNA-Seq data was validated by quantitative real-time PCR of selected differentially expressed genes. Aldehyde dehydrogenase 5A1 (ALDH5A1) which is an enzyme that is involved in mitochondrial glutamate metabolism, was over-expressed in all three DCIS models at both the mRNA and protein levels. Disulfiram and valproic acid are known to inhibit ALDH5A1 and are safe for chronic use in humans for other disorders. Both of these drugs significantly inhibited net proliferation of the DCIS 3D rBM overlay models, but had minimal effect on MCF10A 3D rBM overlay models. These results suggest that ALDH5A1 may play an important role in DCIS and potentially serve as a novel molecular therapeutic target. PMID:23236365

  14. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

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

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  15. Histological Grading in Ductal Carcinoma in Situ of the Breast

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the significance of histological grading as a prognostic factor in ductal carcinoma in situ of the breast. Methods: According to the Van Nuy's classification, 32 cases of ductal carcinoma in situ (DCIS) of the breast were divided into three groups. Results: Low grade (well differentiated, low grade DCIS) 12 patients (37.5%); Intermediate grade, 9 patients (28.1%); High grade (poorly differentiated DCIS) 11 patients (34.4%). Among the high grade DCIS, the histologic subtypes were comedo (9 patients), micropapillary (1 patient) and solid (1 patient). The positive expression of c-erbB-2, p53 and MIB-1 in high grade DCIS was higher than that in intermediate and low grade DCIS. The difference between high grade and low grade DCIS was significant (p<0.05). The expression of ER in high grade DCIS was lower than that in intermediate and low grade DCIS. Conclusions: Histological grading of breast ductal carcinoma in situ may be a good prognostic factor.

  16. 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.

  17. PROGNOSTIC SIGNIFICANCE OF MIB1 PROLIFERATIONMARKER EXPRESSION ON DUCTAL CARCINOMA IN SITU ANDINVASIVE DUCTAL CARCINOMA OF THE BREAST

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To determine the prognostic significance of MIB1 proliferation marker expression on ductal carci noma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Methods By means of histological and immunohis tochemical techniques, MIB1 labelling index (LI) was determined in 31 pathologic specimens (DICS 6, IDC 22 and 3 benign breast lesions as control). Results Significantly higher (P<0.05) MIB1 expression was noted in breast carcinomas in con trast with benign breast lesions. MIB1 LI increased with increasing tumor invasion from DCIS to IDC (P<0.05). Increased tendency of MIB1 LI had been also noted in according with the increased nuclear grading (NG) of IDC. Conclusion MIB1 ex pression can faithfully reflect the proliferative activity of the breast lesions, where the breast cancers with both high MIB1 LI and NG seem to have a poor prognosis.

  18. Infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type: a case series

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    Pervez Shahid

    2007-09-01

    Full Text Available Abstract Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo. However on further histological work up and by using immunohistochemistry (IHC for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS comedo from invasive carcinoma with central necrosis.

  19. Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies

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    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

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

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

    2014-11-15

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

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

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    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.

  2. MicroRNA analysis of breast ductal fluid in breast cancer patients.

    Science.gov (United States)

    Do Canto, Luisa Matos; Marian, Catalin; Willey, Shawna; Sidawy, Mary; Da Cunha, Patricia A; Rone, Janice D; Li, Xin; Gusev, Yuriy; Haddad, Bassem R

    2016-05-01

    Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin specificity. In this study, we have investigated for the first time, through a real-time PCR array, the expression of 742 miRNAs in the ductal lavage fluid collected from 22 women with unilateral breast tumors. We identified 17 differentially expressed miRNAs between tumor and paired normal samples from patients with ductal breast carcinoma. Most of these miRNAs have various roles in breast cancer tumorigenesis, invasion and metastasis, therapeutic response, or are associated with several clinical and pathological characteristics of breast tumors. Moreover, some miRNAs were also detected in other biological fluids of breast cancer patients such as serum (miR-23b, -133b, -181a, 338-3p, -625), plasma (miR-200a), and breast milk (miR-181a). A systems biology analysis of these differentially expressed miRNAs points out possible pathways and cellular processes previously described as having an important role in breast cancer such as Wnt, ErbB, MAPK, TGF-β, mTOR, PI3K-Akt, p53 signaling pathways. We also observed a difference in the miRNA expression with respect to the histological type of the tumors. In conclusion, our findings suggest that miRNA analysis of breast ductal fluid is feasible and potentially very useful for the detection of breast cancer.

  3. Ductal carcinoma in situ and atypical ductal hyperplasia of the breast diagnosed at stereotactic core biopsy.

    Science.gov (United States)

    Méndez, I; Andreu, F J; Sáez, E; Sentís, M; Jurado, I; Cabezuelo, M A; Castañer, E; Gallardo, X; Díaz-Ruiz, M J; López, E; Marco, V

    2001-01-01

    Stereotactic core needle biopsy (SCNB) allows specific histopathologic diagnoses to be made without surgery and has been demonstrated to be an accurate, cost-effective method of diagnosing breast disease, particularly nonpalpable lesions. However, recent studies have concluded that the diagnosis of atypical ductal hyperplasia (ADH) by means of SCNB has resulted in nearly equal odds that a coexisting malignant lesion will be missed. Furthermore, others have concluded that SCNB diagnosed as DCIS cannot reliably indicate the absence of tumor invasion in surgical excision. Between 1993 and 1998, 1,221 consecutive SCNB of mammographically identified lesions were performed using a 14-gauge automated device with an average of 5.3 cores obtained per lesion. ADH was identified in 19 (1.6%) lesions and DCIS in 89 (7.3%). Surgical biopsy was performed in 89 of these patients and histopathologic results from SCNB and surgical biopsies were reviewed and correlated. In 12 cases of ADH diagnosed by SCNB, surgical biopsy showed ADH in 8 (67%) cases and DCIS in the other 4 (33%) cases. In 77 cases of DCIS diagnosed by SCNB, a surgical biopsy showed DCIS in 55 (71%) cases, 6 more cases (8%) had DCIS with focal microinvasion, and 15 (19%) had invasive ductal carcinoma. In one case no residual tumor was found at surgery. In the author's patient population, the diagnosis of ADH at SCNB indicates high probability of DCIS or residual ADH in the surgical biopsy. The diagnosis of DCIS at SCNB is confirmed in the majority of surgical biopsies; however, a significant number of cases may show microinvasion or invasive carcinoma.

  4. Infiltrating ductal carcinoma of the breast presenting as breast abscess : A case report.

    Directory of Open Access Journals (Sweden)

    Vimal Bhandari

    2013-08-01

    Full Text Available Invasive ductal carcinoma, also known as Infiltrating Ductal Carcinoma (IDC is the most common form of breast cancer. IDC starts in the breast\\s milk ducts and invades the surrounding breast stroma. Breast cancer usually present as a: swelling of all or parts of breast, skin irritation or dimpling, breast pain, nipple pain or retraction, redness or scaliness or thickening of the nipple or breast skin, nipple discharge other than breast milk, or a lump in the axilla. We present a case of a 40 year old female, with no family history of malignancy, who underwent Incision and Drainage (I and D for Right Breast Abscess 2 months back followed by a non-healing wound at the I and D site, associated with fungating growth and Right axillary lymph node enlargement, diagnosed as IDC with Axillary lymph node metastasis. Immunohistochemical studies showed deficient basement membrane and myoepithelial layer confirming the infiltrative nature. [Natl J Med Res 2013; 3(4.000: 422-423

  5. Histopathological Features of Invasion of Breast Invasive Ductal Carcinoma and Safety of Breast-conserving Surgery

    Institute of Scientific and Technical Information of China (English)

    Chunping LIU; Huaxiong PAN; Zhi LI; Lan SHI; Tao HUANG

    2009-01-01

    In order to investigate the relationship between the extent of tumor invasion and the tu-mor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery,the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed.The correlation analysis on invasive extent,which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre,and the tumor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and his-tologic grading was processed.There was a significant correlation between invasive extent and tumor size (r=0.766,P0.05),and histologic grading (r=0.228,P>0.05).The 100% negative rate of infiltration in patients without nipple discharge with tumor size 3 cm was obtained at 1.5,2.0 and 2.5 cm away from the tumor respectively.It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.

  6. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Benoit, Vivian; Laenkholm, Anne-Vibeke

    2006-01-01

    to both immunological and endogenous cellular factors, although little is known about the distinct biology of MCB that may contribute to the improved outcome of MCB patients. To identify candidate genes, we performed gene array expression analysis of cell lines of MCB, ductal breast cancer and normal......Medullary breast cancer (MCB) is a morphologically and biologically distinct subtype that, despite cytologically highly malignant characteristics, has a favorable prognosis compared to the more common infiltrating ductal breast carcinoma. MCB metastasizes less frequently, which has been attributed......) 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...

  7. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Benoit, Vivian M; 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...

  8. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Benoit, Vivian; Laenkholm, Anne-Vibeke

    2006-01-01

    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...

  9. Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

    Energy Technology Data Exchange (ETDEWEB)

    Hathout, Lara [Department of Radiation Oncology, Hôpital Maisonneuve-Rosemont, Centre affilié à l' Université de Montréal, Montreal, Quebec (Canada); Hijal, Tarek [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Théberge, Valérie [Department of Radiation Oncology, Centre hospitalier universitaire de Québec, L' Hôtel-Dieu de Québec, Quebec (Canada); Centre des maladies du sein Deschênes-Fabia, Quebec (Canada); Fortin, Bernard [Department of Radiation Oncology, Hôpital Maisonneuve-Rosemont, Centre affilié à l' Université de Montréal, Montreal, Quebec (Canada); Vulpe, Horia [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Hogue, Jean-Charles [Centre des maladies du sein Deschênes-Fabia, Quebec (Canada); Centre hospitalier universitaire de Québec, Hôpital St-Sacrement, Quebec (Canada); Lambert, Christine [Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Bahig, Houda [Department of Radiation Oncology, Hôpital Maisonneuve-Rosemont, Centre affilié à l' Université de Montréal, Montreal, Quebec (Canada); and others

    2013-12-01

    Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. Methods and Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. Results: Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.

  10. Validation of transgenic models of breast cancer: ductal carcinoma in situ (DCIS) and Brca1-mutation-related breast cancer.

    Science.gov (United States)

    Frech, M S; Jones, L P; Furth, P A

    2005-08-01

    Available mouse models of ductal carcinoma in situ (DCIS) and BRCA1-mutation-related breast cancer are reviewed. The best validated mouse models of human DCIS are the conditional estrogen receptor α in mammary tissue (CERM) model initiated by deregulated estrogen receptor α and the serial explant mouse model initiated by p53 deficiency. At present the most useful and best validated mouse model of BRCA1-mutation-related breast cancer uses the cre-lox system to make a conditional Brca1 deletion targeted to mammary epithelial cells. The major shortcoming of the non-conditional Brca1 models is the high incidence of non-mammary tumor development. The use of mammary gland transplants or explants from these mice into nude hosts is one approach that could be used to circumvent this deficiency. Development and validation of a Brca1-mutation-related mouse model of basal cell breast cancer is an important next step.

  11. 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.

  12. Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions

    Directory of Open Access Journals (Sweden)

    Patsouris Effstratios

    2010-07-01

    Full Text Available Abstract Background Hsp90 (heat shock protein90 is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA, atypical ductal hyperplasia (ADH, ductal carcinoma in situ (DCIS and invasive ductal carcinoma (IDC. Methods Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status was conducted in IDC. Results Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031. Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited

  13. MicroRNA analysis of breast ductal fluid in breast cancer patients

    OpenAIRE

    Do Canto, Luisa Matos; Marian, Catalin; WILLEY, SHAWNA; Sidawy, Mary; DA CUNHA, PATRICIA A.; Rone, Janice D.; LI Xin; Gusev, Yuriy; Haddad, Bassem R.

    2016-01-01

    Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin ...

  14. Axillary Metaplastic Breast Carcinoma with Ipsilateral Pectoral Invasive Ductal Carcinoma: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2014-01-01

    Full Text Available We report a case of axillary metaplastic breast carcinoma (MBC with triple negative (ER−/PR−/Her2− phenotype, concurrent with multifocal invasive ductal carcinoma (IDC of ipsilateral pectoral breast (ER+/PR+/Her2− in a 60-year-old woman. The two tumors demonstrate different morphology, immunophenotype, and opposite response to neoadjuvant chemotherapy of paclitaxol, adriamycin, and cyclophosphamide. Methylation analysis of human androgen receptor (HUMARA on X-chromosome identified monoclonal pattern of X-chromosome inactivation in MBC and mosaic pattern in the IDC. Stem cell origin of MBC is suggested in this case. Clinicopathological features, imaging findings, biological markers, chemoradiation management, and prognosis of MBC are reviewed in comparison to invasive ductal carcinoma. Our case and literature review suggest that traditional chemotherapy applicable to IDC is less effective towards MBC. However, new chemotherapy protocols targeting stem cell and multimodality management of MBC are promising. Recognition of unusual presentation of MBC will help tailor therapy towards tumor with worse prognosis.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Ivković-Kapicl Tatjana

    2006-01-01

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

  17. Breast ductoscopy and the evolution of the intra-ductal approach to breast cancer.

    Science.gov (United States)

    Dooley, William C

    2009-01-01

    Interest in breast endoscopy came from Oriental investigators in the early 1990s where bloody nipple discharge is a more common presentation of breast cancer. The early techniques using a single microfiber scope without ductal distension was successful in navigating only the first 1-3 cm of the ducts and fraught with technical problems such as scope breakage and poor image quality. In spite of these barriers there has been increasing use of this technology in Japan and more widespread acceptance as the technology of scope design improved. Dooley and others tested a new method of obtaining a rich cytologic specimen from the ducts of high-risk women known as ductal lavage recently. The success of this procedure was that it detected severe cytologic and malignant atypia in clinically and radiographically normal breasts. Reproducibly, the same breast duct could be cannulated and severely atypical cytology obtained. The problem arose in identifying the lesion within the breast, which was the source for the atypia. New American multi-fiber microendoscopes were applied to solve this problem in an initial series of patients with abnormal cytology to identify the lesions. Success of that series lead to wider application of the imaging technology and eventual adoption of this imaging modality help to guide during all non-mastectomy breast surgery where fluid could be elicited from the nipple to identify the duct connecting to the lesion for which surgery was being performed. Initial reports have demonstrated the types of operative findings in certain sub-populations early in the use of this technology.

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

    Directory of Open Access Journals (Sweden)

    Liu Yan-Xue

    2009-04-01

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

  19. 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

    correlation was found between estimates of vv(nuc) obtained in the in situ component and the invasive part of ductal carcinomas (r = 0.86, 2p = 2.10(-4). Previous studies have shown prognostic value of quantitative histopathological variables in breast carcinomas. The present study points to an additional...

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

    Institute of Scientific and Technical Information of China (English)

    LIU Qun; LI Ji-guang; ZHENG Xin-yu; JIN Feng; DONG Hui-ting

    2009-01-01

    Background 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)-Iike 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.Methods 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.Results 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.Conclusion 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.

  1. Immunohistochemistry applied to the differential diagnosis between ductal and lobular carcinoma of the breast.

    Science.gov (United States)

    de Deus Moura, Rafael; Wludarski, Sheila C L; Carvalho, Filomena M; Bacchi, Carlos E

    2013-01-01

    The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, β-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

  2. Asymptomatic Incidental Ductal Carcinoma in situ in a Male Breast Presenting with Contralateral Gynecomastia

    Directory of Open Access Journals (Sweden)

    Laura M Isley

    2012-01-01

    Full Text Available Ductal carcinoma in situ (DCIS in males is rare and usually presents with symptoms on the affected side, such as, palpable mass or bloody nipple discharge. Even as DCIS has been reported in conjunction with gynecomastia in the same breast, we report an unusual case of a 62-year-old Caucasian male, with no family history of breast cancer, who presented with symptomatic side gynecomastia, and was incidentally found to have DCIS in a completely asymptomatic left breast. To the best of our knowledge, this case is the first report in literature of asymptomatic, incidentally discovered DCIS in a male patient.

  3. 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.

  4. Latissimus Dorsi Flap Invasion by Ductal Breast Carcinoma after Lipofilling

    Directory of Open Access Journals (Sweden)

    Muhannad Alharbi, MD

    2013-11-01

    Full Text Available Summary: Autologous fat grafting is commonly performed in reconstructive breast surgery but also increasingly in breast augmentation surgery. On the international level, we are witnessing an important increased confidence for this procedure. Nevertheless, it continues to raise questions on the risks of cancer. A 66-year-old patient benefited from a lipofilling to improve a latissimus dorsi flap breast reconstruction, 7 years after initial cancer management. Two years later, constant pain in the flap leads to reoperation. The flap showed a major retraction with histologically massive infiltration of the muscle by an undifferentiated carcinoma of breast origin. The tumor cells were displayed directly in contact with lipofilling inside the muscle. Without establishing any causal link between these 2 events, this case raises the question once more of the risks of breast cancer and encourages us to continue being careful.

  5. 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.)

  6. 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.

  7. The role of breast magnetic resonance imaging in the diagnosis of ductal carcinoma in situ

    Directory of Open Access Journals (Sweden)

    Nadrljanski Mirjan

    2013-01-01

    Full Text Available Ductal carcinoma in situ (DCIS, the noninvasive breast malignant tumor originates from the terminal ductal­lobular units (TDLU. The typical feature of DCSI is the formation of calcifications. Up to 90% of DCIS are diagnosed on mammographic examinations, as clinically asymptomatic. Between 10% and 20% of DCIS remain mammographically occult due to the lack of calcifications and/ or small tumor dimensions. Contrast­enhanced breast magnetic resonance imaging (MRI detects mammographically occult breast lesions, thus defining morphologic features of the lesion and the dynamics of signal intensity changes due to contrast enhancement. Distribution of contrast enhancement - signal intensity increase in DCIS most frequently includes segmental, ductal and linear patterns, followed by regional enhancement pattern, while the intralesional contrast uptake most frequently includes the nodular pattern with the areas of confluence. Post­ contrast signal intensity increase in DCIS is most frequently fast in the initial phase (wash­in, while the whole dynamic of contrast­enhancement includes either of the three possible time­intensity curve (TIC types (persistent, plateau or washout, although the plateau TIC is considered to be more frequent. Breast MRI has high sensitivity in the diagnosis of invasive breast cancer, varying from 90% to 100%; the sensitivity in the diagnosis of DCIS is lower (77­96%. For the time being, the primary role of MRI in DCIS is planning of breast­conserving surgery (BCS for the evaluation of lesion extension. Further development of MRI in the diagnosis of DCIS includes the implementation of the principles of functional and molecular imaging.

  8. Risk of subsequent invasive breast cancer after a diagnosis of ductal carcinoma in situ (DCIS).

    Science.gov (United States)

    Cheung, Shan; Booth, Mary E; Kearins, Olive; Dodwell, David

    2014-12-01

    Despite surgical removal of ductal carcinoma in situ (DCIS), recurrences still occur. This retrospective cohort study evaluated the risk of invasive recurrence following surgery and investigated factors which may be predictive of recurrence. We specifically investigated invasive recurrence with respect to mode of detection of DCIS. Patients whose DCIS was detected outside of the NHS Breast Screening Programme have a higher risk of subsequent ipsilateral invasive breast cancer than those whose DCIS is detected through screening. There is no significant difference in risk of subsequent contralateral invasive recurrence according to mode of detection.

  9. MR imaging of mucinous carcinoma of the breast associated with ductal carcinoma in situ: case report

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    Kim, Youn Jeong; Kim, Mi Young; Cho, Young Up; Kim, Sei Joong; Kim, Won Hong; Suh, Chang Hae; Han, Jee Young [Inha University Hospital, Incheon (Korea, Republic of)

    2007-01-15

    A mucinous carcinoma of the breast is an uncommon carcinoma containing mucin that is associated with a mucocele-like tumor or other malignant tumors. We report the MR imaging findings of two cases, a mucinous carcinoma and ductal carcinoma in situ (DCIS), associated with mucocele-like tumor. The mucinous carcinoma showed a gradually enhancing kinetic pattern on the dynamic MR and high signal intensity on the T2-weighted images. The MR findings were indistinguishable from a common benign mass of the breast.

  10. 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.

  11. 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

    the Danish National Patient Registry that were cross-checked with the Danish Breast Cancer Group database and the Danish Pathology Register. Main Outcomes and Measures: Reoperation rate after wire-guided BCS in patients with IBC or DCIS. Results: Wire-guided BCS was performed in 4118 women (mean [SD] age, 60......Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs...... to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS...

  12. Appraisal of the technologies and review of the genomic landscape of ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Pang, Jia-Min B; Gorringe, Kylie L; Wong, Stephen Q; Dobrovic, Alexander; Campbell, Ian G; Fox, Stephen B

    2015-06-16

    Ductal carcinoma in situ is a biologically diverse entity. Whereas some lesions are cured by local surgical excision, others recur as in situ disease or progress to invasive carcinoma with subsequent potential for metastatic spread. Reliable prognostic biomarkers are therefore desirable for appropriate clinical management but remain elusive. In common with invasive breast cancer, ductal carcinoma in situ exhibits many genomic changes, predominantly copy number alterations. Although studies have revealed the genomic heterogeneity within individual ductal carcinoma in situ lesions and the association of certain copy number alterations with nuclear grade, none of the genomic changes defined so far is consistently associated with invasive transformation or recurrence risk in pure ductal carcinoma in situ. This article will review the current landscape of genomic alterations in ductal carcinoma in situ and their potential as prognostic biomarkers together with the technologies used to define these.

  13. 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.

  14. 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.

  15. 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.

  16. Generation of Rat Monoclonal Antibodies Against Human Pancreatic Ductal Adenocarcinoma Cells.

    Science.gov (United States)

    Higashi, Kiyoshi; Fujii, Nobuaki; Kushida, Masahiko; Yamada, Keita; Suzuki, Noriyuki; Saito, Koichi; Tachibana, Taro

    2016-06-01

    Pancreatic ductal adenocarcinoma is an aggressive tumor with a poor prognosis. Biomarkers that can detect the tumor in its early stages when it may be amenable to curative resection might improve prognosis. To discover novel markers expressed in primary pancreatic cancer, we generated a panel of monoclonal antibodies against pancreatic ductal adenocarcinoma cell line BxPC3 using a rat medial iliac lymph node method. The antigen recognized by 1B5A5 was expressed on the cell surface and secreted into the conditioned medium of BxPC3 cells, and characterized as glycoproteins with molecular mass between 60 and 90 kDa. A wide range of molecular weights of 1B5A5 antigen in several pancreatic cancer cell lines were observed. Immunohistochemistry using a human multiple organ tumor tissue array showed an enhanced expression of 1B5A5 antigen in pancreas, lung, stomach, breast, urinary bladder, colon, and cervix uteri cancers. Immunoprecipitation followed by proteomic analyses identified CEACAM6 as a 1B5A5 antigen. In addition, western blot analysis results indicated that the 1B5A5 epitope is located within an amino-terminal domain of CEACAM6. These results raised the possibility that our approach could lead to discovery of novel biomarkers for the early stage of cancers in a relatively short period of time.

  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...... 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. 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...... 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...

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

    Science.gov (United States)

    2009-02-01

    Burstein, HJ, Polyak , K, Wong, JS, Lester, SC and Kaelin, CM. Ductal Carcinoma in Situ of the Breast. N Engl J Med 350:1430-41, 2004. 4. Page DL, Dupont...nodeT a b le 1 . C h a ra ct er is ti cs o f tu m o r ti ss u es S et a N S iz e (m m ) N o d e in v o lv em en t T N M st a g e N u m b er o f d ea th s

  20. Basal cytokeratin phenotypes of myoepithelial cells indicates the origin of ductal carcinomas in situ of the breast.

    Science.gov (United States)

    Chen, Ling; Yin, Xiaona; Lu, Shanshan; Chen, Guorong; Dong, Lei

    2015-09-01

    Terminal duct lobular unit (TDLU) is widely accepted as the origin of ductal carcinoma in situ of breast. The differentiation states of myoepithelial cells of breast ductal system hint the development of breast hyperplastic lesions. Basal cytokeratin (CK) phenotypes indicate the differentiation of myoepithelial cells. Using antibodies of CK5/6, CK14, and CK17, this study reports the basal CK phenotypes of myoepithelial cells in 20 foci of normal breast, 20 usual ductal hyperplasias, 36 ductal carcinomas in situ (DCIS), and 28 sclerosing adenosis (SA). The results showed that the positive staining of basal CKs of myoepithelial cells in normal ducts were significantly higher than those in normal lobules. The basal CK expression of myoepithelial cells of DCIS and usual ductal hyperplasia was similar to that of normal duct, whereas that of SA was similar to that of normal lobule. We propose a modified model of TDLU origin of intraductal carcinoma that most of DCIS originate from terminal ducts of TDLU, whereas most SA originate from lobules.

  1. Breast ductal carcinoma in situ carry mutational driver events representative of invasive breast cancer.

    Science.gov (United States)

    Pang, Jia-Min B; Savas, Peter; Fellowes, Andrew P; Mir Arnau, Gisela; Kader, Tanjina; Vedururu, Ravikiran; Hewitt, Chelsee; Takano, Elena A; Byrne, David J; Choong, David Yh; Millar, Ewan Ka; Lee, C Soon; O'Toole, Sandra A; Lakhani, Sunil R; Cummings, Margaret C; Mann, G Bruce; Campbell, Ian G; Dobrovic, Alexander; Loi, Sherene; Gorringe, Kylie L; Fox, Stephen B

    2017-03-24

    The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30). TP53 mutations were exclusive to high grade DCIS and more frequent in PR-negative tumors compared with PR-positive tumors (P=0.037). TP53 mutant tumors also had a significantly higher fraction of the genome altered by copy number than wild-type tumors (P=0.005), including a significant positive association with amplification or gain of ERBB2 (P<0.05). The association between TP53 mutation and ERBB2 amplification was confirmed in a wider DCIS cohort using p53 immunohistochemistry as a surrogate marker for TP53 mutations (P=0.03). RUNX1 mutations and MAP2K4 copy number loss were novel findings in DCIS. Frequent copy number alterations included gains on 1q, 8q, 17q, and 20q and losses on 8p, 11q, 16q, and 17p. Patterns of genomic alterations observed in DCIS were similar to those previously reported for invasive breast cancers, with all DCIS having at least one bona fide breast cancer driver event. However, an increase in GATA3 mutations and fewer copy number changes were noted in DCIS compared with invasive carcinomas. The role of such alterations as prognostic and predictive biomarkers in DCIS is an avenue for further investigation.Modern Pathology advance online publication, 24 March 2017; doi:10.1038/modpathol.2017.21.

  2. The Value of p63 and CK5/6 Expression in the Differential Diagnosis of Ductal Lesions of Breast

    Institute of Scientific and Technical Information of China (English)

    DING Yanping; RUAN Qiurong

    2006-01-01

    In order to explore the value of p63, smooth muscle actin (α-SMA) and cytokeratin 5/6(CK5/6) in the differential diagnosis of ductal lesions of breast, 88 tissue specimens of ductal lesions of breast were collected and examined histologically by HE staining. By using immunohistochemistry,the expression of p63, α-SMA and CK5/6 was detected. The results showed that in 38 cases of benign breast lesions, the proliferating cells were all positive for p63 and α-SMA. In 19 cases of ductal carcinoma in situ (DCIS) and 7 cases of intraductal papillary carcinoma, α-SMA positive cells formed a layer of continuous embroider-shaped structure and the p63 positive cells formed a layer of evenly separated embroider-shaped structure around the ducts. There was no cross-reaction between p63 and interstitial myofibroblasts and vascular smooth muscle cells. In 38 cases of benign breast lesions, the positive rate of CK5/6 expression was 100 %. In 5 cases of atypical ductal hyperplasia, there were few positive cells in the ducts. In 19 cases of CDIS, no tumor cells expressed CK5/6. In 19 cases of invasive ductal carcinoma, almost no CK5/6 was detectable. It was suggested that p63 could serve as a novel specific marker for the identification of breast myoepithelial cells. CK5/6 is of value in differentiating ductal proliferation of varying degrees, especially in the differentiation between cancerous and non-cancerous changes. Simultaneous detection of p63, CK5/6 and α-SMA can help increase the diagnostic accuracy of breast diseases.

  3. 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.

  4. A rare case of male breast ductal carcinoma in-situ associated with prolactinoma.

    Science.gov (United States)

    Mallawaarachchi, Chandike Maithri; Ivanova, Snezana; Shorthouse, Alice; Shousha, Sami; Sinnett, Dudley

    2011-08-31

    A case of ductal carcinoma in-situ (DCIS) associated with prolactinoma in a male patient is described. A 56-year-old gentleman presented with lethargy and loss of libido. His prolactin at presentation was 3680 mU/l and an MRI scan of the head revealed a pituitary tumour suggestive of prolactinoma. Following 18 months of treatment with cabergoline, the prolactin level reduced to 914 mU/l. However, 3 years later he presented with blood stained nipple discharge, the cytology of which was negative for cancer. Ultrasound scan of his right breast revealed a single dilated mammary duct. Microdochectomy was performed. The histology revealed incompletely excised DCIS. There is increasing evidence of prolactinoma associated with breast cancer with or without DCIS in females. A review of the literature reveals only one previous case report of this association in males. This is the first case of pure DCIS preceded by prolactinoma in a male patient.

  5. Symmetrical ethmoidal metastases from ductal carcinoma of the breast, suggesting transcribrosal spread.

    Science.gov (United States)

    Monserez, D; Vlaminck, S; Kuhweide, R; Casselman, J

    2001-01-01

    Symmetrical ethmoidal metastases from ductal carcinoma of the breast, suggesting transcribrosal spread. While half of breast cancers develop metastases, the appearance of metastatic disease in paranasal sinuses from this origin is very rare. Eighteen other cases were found in the literature, dating from 1939 till now. A case of metastatic breastcancer presenting as a subacute therapy-resistant pansinusitis is described. The perfect symmetry was misleading. Bilateral ethmoidal biopsies were compatible with metastases from a ductal adenocarcinoma. Further investigation revealed meningeal carcinomatosis in the supra-orbital region and locoregional recurrence in the mastectomy scar and axilla. Comparing these 19 cases in chronological order, it was noticed that symptoms at time of diagnosis shift from those of space occupying lesions to those suggestive for sinusitis. This shift could be explained by earlier diagnosis. High index of suspicion is the key to diagnosis. Earlier diagnosis does not result in longer survival since in most cases patients have already widespread disease and die within one year. Most authors mention the role of the vertebral venous plexus in hematogeneous spreading of tumor cells. Another pathway of hematogenous spread is via (occult) lung metastases. This case prompts the hypothesis of transcribrosal spread from meningeal involvement.

  6. Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach.

    NARCIS (Netherlands)

    Flucke, U.E.; Flucke, M.T.; Hoy, L.; Breuer, E.; Goebbels, R.; Rhiem, K.; Schmutzler, R.; Winzenried, H.; Braun, M.; Steiner, S.; Buettner, R.; Gevensleben, H.

    2010-01-01

    AIMS: Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. O

  7. 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.

  8. Nuclear expression of KLF6 tumor suppressor factor is highly associated with overexpression of ERBB2 oncoprotein in ductal breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Ricardo C Gehrau

    Full Text Available BACKGROUND: Krüppel-like factor 6 (KLF6 is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues in a microarray format representing fifteen human organs. Results indicate that while both nuclear and cytoplasmic distribution of KLF6 is detected in normal breast tissues, breast carcinomas express KLF6 mainly detected in the cytoplasm. Expression of KLF6 was further analyzed in breast cancer tissues overexpressing ERBB2 oncoprotein, which is associated with poor disease prognosis and patient's survival. The analysis of 48 ductal carcinomas revealed a significant population expressing KLF6 predominantly in the nuclear compartment (X(2p = 0.005; Fisher p = 0.003. Moreover, this expression pattern correlates directly with early stage and small ductal breast tumors and linked to metastatic events in lymph nodes. CONCLUSIONS/SIGNIFICANCE: Data are consistent with a preferential localization of KLF6 in the nuclear compartment of early stage and small HER2-ERBB2 overexpressing ductal breast tumor cells, also presenting lymph node metastatic events. Thus, KLF6 tumor suppressor could represent a new molecular marker candidate for tumor prognosis and/or a potential target for therapy strategies.

  9. A case of renal cell carcinoma metastasizing to invasive ductal breast carcinoma

    Directory of Open Access Journals (Sweden)

    Tai-Di Chen

    2014-02-01

    Full Text Available Tumor-to-tumor metastasis is an uncommon but well-documented phenomenon. We present a case of a clear cell renal cell carcinoma (RCC metastasizing to an invasive ductal carcinoma (IDC of the breast. A 74-year-old woman with a past history of clear cell RCC status after radical nephrectomy underwent right modified radical mastectomy for an enlarging breast mass 3 years after nephrectomy. Histological examination revealed a small focus with distinct morphological features similar to clear cell RCC encased in the otherwise typical IDC. Immunohistochemical studies showed that this focus was positive for CD10 and vimentin, in contrast to the surrounding IDC, which was negative for both markers and positive for Her2/neu. Based on the histological and immunohistochemical features, the patient was diagnosed with metastasis of clear cell RCC to the breast IDC. To the best of our knowledge, this is the first reported case of a breast neoplasm as the recipient tumor in tumor-to-tumor metastasis.

  10. The Polycomb group protein RING1B is overexpressed in ductal breast carcinoma and is required to sustain FAK steady state levels in breast cancer epithelial cells

    Science.gov (United States)

    Bosch, Almudena; Panoutsopoulou, Konstantina; Corominas, Josep Maria; Gimeno, Ramón; Moreno-Bueno, Gema; Martín-Caballero, Juan; Morales, Saleta; Lobato, Tania; Martínez-Romero, Carles; Farias, Eduardo F.; Mayol, Xavier; Cano, Amparo; Hernández-Muáoz, Inmaculada

    2014-01-01

    In early stages of metastasis malignant cells must acquire phenotypic changes to enhance their migratory behavior and their ability to breach the matrix surrounding tumors and blood vessel walls. Epigenetic regulation of gene expression allows the acquisition of these features that, once tumoral cells have escape from the primary tumor, can be reverted. Here we report that the expression of the Polycomb epigenetic repressor Ring1B is enhanced in tumoral cells that invade the stroma in human ductal breast carcinoma and its expression is coincident with that of Fak in these tumors. Ring1B knockdown in breast cancer cell lines revealed that Ring1B is required to sustain Fak expression in basal conditions as well as in Tgfβ-treated cells. Functionally, endogenous Ring1B is required for cell migration and invasion in vitro and for in vivo invasion of the mammary fat pad by tumoral cells. Finally we identify p63 as a target of Ring1B to regulate Fak expression: Ring1B depletion results in enhanced p63 expression, which in turns represses Fak expression. Importantly, Fak downregulation upon Ring1B depletion is dependent on p63 expression. Our findings provide new insights in the biology of the breast carcinoma and open new avenues for breast cancer prognosis and therapy. PMID:24742605

  11. Patterns of care for ductal carcinoma in situ of the breast: Queensland's experience over a decade.

    Science.gov (United States)

    Barbour, Samantha; Moore, Julie; Dunn, Nathan; Effeney, Rachel; Harden, Hazel; McCarthy, Alexandra; Walpole, Euan; Lehman, Margot

    2017-10-01

    To review management of ductal carcinoma in situ (DCIS) of the breast in Queensland, with reference to breast conserving surgery (BCS) and adjuvant radiation therapy (RT). In addition, we examined the incidence of invasive breast cancer recurrence and factors predictive of invasive recurrence. A retrospective review of the Queensland Oncology Repository identified women with resected DCIS (TisN0) ± adjuvant RT between 2003 and 2012. Time to invasive breast cancer recurrence was analysed using the Kaplan Meier method. Median follow-up was 4.9 years. 3038 women had surgery. 940 (31%) had mastectomy and 2098 (69%) underwent BCS. Of 2098 women having BCS, 1100 (52%) received BCS alone and 998(48%) received adjuvant RT. The use of RT significantly increased over the decade from 25% to 62% (p=<0.001). Clinicopathological factors associated with RT use on multivariate analysis included age ≤70, higher socioeconomic status, larger tumour size, higher nuclear grade and surgical margins ≤5 mm. Invasive breast cancer recurrence at 5 years was 1.7% [95% CI 1.0-3.0] in RT group versus 2.8% [95% CI 2.1-3.8] in BCS alone group. Factors associated with increased risk of invasive recurrence on multivariate analysis were age <40 and surgical margins ≤2 mm. The use of adjuvant RT in Queensland significantly increased between 2003 and 2012. Selection of patients for RT was based on clinicopathological factors associated with higher recurrence risk. Although longer follow-up is required, the selective use of radiation therapy after BCS is associated with a low rate of invasive breast cancer recurrence at 5 years. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. 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...... at 5x magnifications was the most efficient considering data load and time consumption. Discussion and conclusion: The need for biomarkers is obvious and reliable measurements are crucial to enable application in clinical trials and routine settings. We described a method to gain reproducible...

  13. Myc promoter-binding protein-1 (MBP-1 is a novel potential prognostic marker in invasive ductal breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Mariavera Lo Presti

    Full Text Available BACKGROUND: Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. α-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1 originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of α-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken. METHODOLOGY AND FINDINGS: We analyzed α-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-α-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic α-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC. CONCLUSIONS: MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer.

  14. Correlation of expression of ER,PR and c-erbB-2 with ultrasonographic features in invasive ductal cancer of breast

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze the relationship of the expression level of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2,c-erbB-2)of breast invasive ductal carcinoma(IDC)with ultrasonographic characteristics.Methods Totally 104 patients with IDCs confirmed pathologically were involved in this study.ER,PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique.The correlation between the ultrasonographic features and the ...

  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 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.

  17. 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.

  18. 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

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

    Science.gov (United States)

    Laurinavicius, Arvydas; Laurinaviciene, Aida; Ostapenko, Valerijus; Dasevicius, Darius; Jarmalaite, Sonata; Lazutka, Juozas

    2012-03-16

    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. 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). 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 variation. Finally, we

  20. 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.)

  1. Initiation of metastatic breast carcinoma by targeting of the ductal epithelium with adenovirus-cre: a novel transgenic mouse model of breast cancer.

    Science.gov (United States)

    Rutkowski, Melanie R; Allegrezza, Michael J; Svoronos, Nikolaos; Tesone, Amelia J; Stephen, Tom L; Perales-Puchalt, Alfredo; Nguyen, Jenny; Zhang, Paul J; Fiering, Steven N; Tchou, Julia; Conejo-Garcia, Jose R

    2014-03-26

    Breast cancer is a heterogeneous disease involving complex cellular interactions between the developing tumor and immune system, eventually resulting in exponential tumor growth and metastasis to distal tissues and the collapse of anti-tumor immunity. Many useful animal models exist to study breast cancer, but none completely recapitulate the disease progression that occurs in humans. In order to gain a better understanding of the cellular interactions that result in the formation of latent metastasis and decreased survival, we have generated an inducible transgenic mouse model of YFP-expressing ductal carcinoma that develops after sexual maturity in immune-competent mice and is driven by consistent, endocrine-independent oncogene expression. Activation of YFP, ablation of p53, and expression of an oncogenic form of K-ras was achieved by the delivery of an adenovirus expressing Cre-recombinase into the mammary duct of sexually mature, virgin female mice. Tumors begin to appear 6 weeks after the initiation of oncogenic events. After tumors become apparent, they progress slowly for approximately two weeks before they begin to grow exponentially. After 7-8 weeks post-adenovirus injection, vasculature is observed connecting the tumor mass to distal lymph nodes, with eventual lymphovascular invasion of YFP+ tumor cells to the distal axillary lymph nodes. Infiltrating leukocyte populations are similar to those found in human breast carcinomas, including the presence of αβ and γδ T cells, macrophages and MDSCs. This unique model will facilitate the study of cellular and immunological mechanisms involved in latent metastasis and dormancy in addition to being useful for designing novel immunotherapeutic interventions to treat invasive breast cancer.

  2. Characterization of ductal carcinoma in situ on diffusion weighted breast MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rahbar, Habib; Partridge, Savannah C.; Eby, Peter R.; DeMartini, Wendy B.; Gutierrez, Robert L.; Peacock, Sue; Lehman, Constance D. [University of Washington, Seattle Cancer Care Alliance, Department of Radiology, Seattle, WA (United States)

    2011-09-15

    To characterize ductal carcinoma in situ (DCIS) and its subtypes on diffusion-weighted imaging (DWI). We retrospectively reviewed 74 pure DCIS lesions in 69 women who underwent DWI at 1.5 T (b = 0 and 600 s/mm{sup 2}). Each lesion was characterized by qualitative DWI intensity, quantitative DWI lesion-to-normal contrast-to-noise ratio (CNR), and quantitative apparent diffusion coefficient (ADC). The detection rate was calculated with predetermined thresholds for each parameter. The effects of lesion size, grade, morphology, and necrosis were assessed. Ninety-six percent (71/74) of DCIS lesions demonstrated greater qualitative DWI intensity than normal breast tissue. Quantitatively, DCIS lesions demonstrated on average 56% greater signal than normal tissue (mean CNR = 1.83 {+-} 2.7) and lower ADC values (1.50 {+-} 0.28 x 10{sup -3} mm{sup 2}/s) than normal tissue (2.01 {+-} 0.37 x 10{sup -3} mm{sup 2}/s, p < 0.0001). A 91% detection rate was achieved utilizing an ADC threshold (<1.81 x 10{sup -3} mm{sup 2}/s). Non-high-grade DCIS exhibited greater qualitative DWI intensity (p = 0.02) and quantitative CNR (p = 0.01) than high-grade DCIS but no difference in ADC (p = 0.40). Lesion size, morphology, and necrosis did not affect qualitative or quantitative DWI parameters of DCIS lesions (p > 0.05). DCIS lesions have higher DWI signal intensity and lower ADC values than normal breast tissue. DWI warrants further investigation as a potential non-contrast MRI tool for early breast cancer detection. (orig.)

  3. Value of ductal obstruction sign in the differentiation of benign and malignant breast lesions at MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Baltzer, P.A.T., E-mail: pascal.baltzer@med.uni-jena.d [Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07740 Jena (Germany); Kaiser, C.G.N.; Dietzel, M.; Vag, T.; Herzog, A.B. [Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07740 Jena (Germany); Gajda, M. [Institute of Pathology, Friedrich-Schiller-University Jena, Ziegelmuehlenweg 1, D-07740 Jena (Germany); Camara, O. [Clinic of Gynecology, Friedrich-Schiller-University Jena, Bachstr. 18, D-07740 Jena (Germany); Kaiser, W.A. [Institute of Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Erlanger Allee 101, D-07740 Jena (Germany)

    2010-08-15

    Purpose: : MR-Mammography (MRM) is regarded as the most sensitive method for detection of breast cancer without a broad consensus on specificity. There is room for improvement of the existing ACR BIRADS lexicon by adding new and specific descriptors. Dilated ducts have been described in association with papillomas. However, the differential diagnostic value of this finding has not been investigated yet. Materials and methods: : 316 consecutive patients, undergoing histopathologic workup after MR-Mammography were included in this prospective, ethical review board approved study. Two blinded radiologists rated the images in consensus. Ductal obstruction was defined as dilated liquid filled ducts proximal an enhancing lesion. Sensitivity, specificity as well as positive and negative likelihood ratio (LR+, LR-) were calculated. Results: Dilated ducts were found in 60 cases (19%), 20 of these showed an association with enhancing lesions and were categorized as ductal obstruction (6.3%). Malignancy was found in two cases (one invasive ductal carcinoma and one DCIS) and benign tissue in 18 cases (15 papillomas). The difference of ductal obstruction between these groups was found to be highly significant in two-sided Fisher's exact test (p < 0.001). Because of the clear association with benign lesions, benign lesions showing ductal obstruction were characterized as true positive findings. Therefore, following diagnostic parameters were calculated: sensitivity 15.4%, specificity 99.0%, LR+ 15.3, LR- 0.9. Discussion: If ductal obstruction is found to be positive, the associated lesion is most likely benign. Therefore, though a rare finding, this descriptor should be taken into account for improved lesion differentiation.

  4. [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.

  5. Expression of Presenilin-2 and Glutathione S Transferase π and Their Clinical Significance in Breast Infiltrating Ductal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    FANWei; WUXiaoting; ZHOUYejiang; ZHOUTong; HUANGXiong

    2005-01-01

    Objective: To investigate the expressions of presenilin-2 (PS2) and glutathione S transferase π (GSTπ) and their roles in prognosis and therapy of breast infiltrating ductal carcinoma. Methods:The paraffin-embedded specimens of 210 patients with breast infiltrating ductal carcinoma were examined by using LSAB immunohistochemistry for the expression of PS2 and GSTπ. Results: The expression rate of PS2 and GSTπ was 49.5% (104/210) and 48.1% (101/210) respectively. The 5-year and 10-year postoperative survival rates in 4 groups, from high to low, were group 1 (PS2 positive expression/GSTπ negative expression), group 2 (PS2 positive expression/GSTπ positive expression), group 3 (PS2 negative expression/GSTπ negative expression) and group 4 (PS2 negative expression/GSTπ positive expression) in turn. Conclusion: The prognosis of the group 1 was the best, followed by the group 2, group 3 and group 4 in turn. These results suggested that the reasonable use of endocrinotherapy and chemotherapy for patients with breast infiltrating ductal carcinoma is necessary.

  6. Sonographic findings of ductal carcinoma in situ of the breast : comparison with mammographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eung Yeop; Han, Boo-Kyung; Choe, Yeon Hyeon; Nam, Seok Jin; Ko, Young Hyeh; Yang, Jung Hyun [Samsung Medical Center, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-12-01

    To evaluate the sonographic findings and detection rate of ductal carcinoma in situ (DCIS) and to compare the results with mammographic findings. Of 134 patients with pathologically proven DCIS, 47 patients (48 breasts) who underwent sonography before surgery were included. Twenty-seven patients were asymptomatic, while 20 experienced symptoms. Whether a lesion was present, and the nature of the related sonographic finding were analyzed retrospectively. When a mass was identified by means of sonography, it was evaluated in terms of its shape, margin, echogenicity, associated microcalcifications, and intervening echogenic lines. Sonography detected 39/48 cases of DCIS (81%). In 24 cases, detection was based only on the presence of the mass, while in nine cases this depended on additional findings alone [periductal thickening (n=6);micronodules (n=3)]. In three cases the presence of microcalcifications alone was sufficient for detecton and in the other three cases, detection was based on the presence of microcalcifications as well as on additional findings [periductal thickening (n=2); micronodules (n=1)]. Thirteen lesions (54%) were irregular in shape, while 11 (46%) were o val or lobulated. The margins of 17 lesions (71%) were ill-defined, and in 18 (75%), echogenicity was slightly hypoechoic. Sonography showed that for masses identified as DCIS, the most common findings were an ill-de-fined margin, irregular shape, and mild hypoechogenicity. Microcalcifications were identified in 13 of 48 breasts (27%), while in some cases intervening echogenic lines and microcalcifications were the only finding. For early detection of DCIS, mammography together with sonography may be helpful.

  7. 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.

  8. Necrotizing granulomatous inflammation in an ipsilateral axillary lymph node in a patient with invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Yang, Limin; Park, Jeong Mi; Askeland, Ryan W; Fajardo, Laurie L

    2012-01-01

    A patient presented with flu-like symptoms and a warm, tender area in the left axilla after working with an ancient piece of Cyprus wood. Antibiotics prescribed failed to improve symptoms. Followup physical examination and subsequent ultrasound found suspicious left-breast mass and an enlarged lymph node in the left axilla. Biopsy and lumpectomy of the left-breast mass revealed invasive ductal carcinoma. Biopsy and excision of the enlarged lymph node in the left axilla revealed necrotizing granulomatous inflammation without evidence of metastatic breast carcinoma. To our knowledge, this is the first case report to show the coexistence of breast cancer with necrotizing granulomatous inflammation in the ipsilateral axillary lymph node, likely due to exposure to ancient wood.

  9. 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, H.; Horlings, H.M.; Vegt, B. van der; Kreike, B.; Ajouaou, A.; Vijver, M.J. van de; Marike Boezen, H.; Bock, G.H. de; Graaf, W.T. van der; Wesseling, J.

    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 carc

  10. 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 carc

  11. Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.

    Science.gov (United States)

    Lacroix-Triki, Magali; Suarez, Paula H; MacKay, Alan; Lambros, Maryou B; Natrajan, Rachael; Savage, Kay; Geyer, Felipe C; Weigelt, Britta; Ashworth, Alan; Reis-Filho, Jorge S

    2010-11-01

    Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the

  12. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.

    Science.gov (United States)

    Wang, Shi-Yi; Long, Jessica B; Killelea, Brigid K; Evans, Suzanne B; Roberts, Kenneth B; Silber, Andrea; Gross, Cary P

    2016-07-01

    Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94 years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p clinically evident.

  13. Rapidly growing complex fibroadenoma with surrounding ductal hyperplasia mimics breast malignancy on serial F-18 FDG PET/CT imaging.

    Science.gov (United States)

    Makis, William; Ciarallo, Anthony; Hickeson, Marc; Derbekyan, Vilma

    2011-07-01

    A 30-year-old woman was referred for an F-18 fluorodeoxyglucose (FDG) PET/CT to rule out lymphoma, and was found to have an incidental FDG-avid right breast nodule that grew significantly in size and FDG uptake on a subsequent scan, raising suspicion of a growing breast malignancy. Histologic evaluation showed a complex fibroadenoma with adenosis and surrounding ductal hyperplasia. Although variable F-18 FDG uptake in fibroadenomas has been described, a distinction between simple and complex fibroadenomas has not been made in the PET literature, even though complex fibroadenomas have a higher propensity to develop into malignancies. This case shows that a rapidly growing complex fibroadenoma can mimic a breast malignancy on serial F-18 FDG PET/CT scans, showing significant increase in both size and FDG-avidity on follow-up studies.

  14. Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Dallol, Ashraf; Buhmeida, Abdelbaset; Merdad, Adnan; Al-Maghrabi, Jaudah; Gari, Mamdooh A; Abu-Elmagd, Muhammad M; Elaimi, Aisha; Assidi, Mourad; Chaudhary, Adeel G; Abuzenadah, Adel M; Nedjadi, Taoufik; Ermiah, Eramah; Alkhayyat, Shadi S; Al-Qahtani, Mohammed H

    2015-12-01

    Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context.

  15. Bilateral mucocele-like tumors of the breast associated with ductal carcinoma in situ and mucinous carcinoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jeong Hee; Kim, Hak Hee; Shin, Hee Jung; Kim, Mi Jung; Baek, Mun Hee; Kim, Dae Bong [Asan Medical Center, University of Ulsan, College of Medicine, Seoul (Korea, Republic of)

    2006-01-15

    Mucocele-like tumor of the breast is a rare neoplasm and only a few cases of mucocele-like tumor have been reported on the Korea. These lesions were originally considered as being benign when they were first described, but now it is believed they can be both malignant and benign, and it is even possible that they are early lesions of mucinous carcinoma. We describe here both the mammographic and sonographic findings in a patient with bilateral mucocele-like tumors that were associated with ductal carcinoma in situ and mucinous carcinoma.

  16. Ductal Carcinoma in Situ of the Breast: Evaluating the Role of Radiation Therapy in the Management and Attempts to Identify Low-Risk Patients

    OpenAIRE

    Shah,Chirag; Vicini, Frank A.; Berry, Sameer; Julian, Thomas B.; Ben Wilkinson, J.; Shaitelman, Simona F.; Khan, Atif; Finkelstein, Steven E.; Goldstein, Neal

    2015-01-01

    Ductal carcinoma in-situ (DCIS) of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with DCIS include mastectomy or breast-conserving therapy (BCT). While several randomized trials have confirmed a greater than 50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared to breast-conserving surgery (BCS) alone, controversy ...

  17. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  18. Intensity Modulated Accelerated Partial Breast Irradiation Before Surgery in Treating Older Patients With Hormone Responsive Stage 0-I Breast Cancer

    Science.gov (United States)

    2016-05-04

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Lobular Breast Carcinoma in Situ; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Tubular Ductal Breast Carcinoma

  19. Cigarette smoking in relation to risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Kim, Mimi; Kakani, Chandana; Tindle, Hilary; Wactawski-Wende, Jean; Ockene, Judith K; Luo, Juhua; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2010-09-01

    In numerous studies, investigators have examined the association of active smoking with risk of invasive breast cancer, but to the authors' knowledge, no cohort study has assessed smoking in relation to the risk of in situ breast cancer, the postulated penultimate stage preceding invasive breast cancer. The authors examined the latter association using data collected at baseline from 63,393 women in the Women's Health Initiative Clinical Trial. A total of 486 cases of ductal carcinoma in situ (DCIS) of the breast were identified during 8 years of follow-up between 1993 and 2005. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. For the primary analysis, invasive breast cancer was treated as a competing risk. After adjustment for covariates, associations with smoking status, smoking intensity, duration, pack-years, and age at quitting were all close to the null value and showed few meaningful trends. Sensitivity analyses performed to address different possibilities with respect to the natural history of breast cancer also did not provide consistent evidence of an association of smoking with DCIS. The results of this large cohort study provide little support for an association of cigarette smoking with risk of DCIS in postmenopausal women.

  20. SPARC (osteonectin) in breast tumors of different histologic types and its role in the outcome of invasive ductal carcinoma.

    Science.gov (United States)

    Hsiao, Yi-Hsuan; Lien, Huang-Chun; Hwa, Hsiao-Lin; Kuo, Wen-Hung; Chang, King-Jen; Hsieh, Fon-Jou

    2010-01-01

    The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Secreted protein acidic and rich in cystein was not expressed in benign breast phylloides and all benign breast tumors, while expressed in 17.2% of IDC, 85% of metaplastic carcinoma of the breast (MCB), and all malignant breast phylloides. Secreted protein acidic and rich in cystein was strongly expressed in mesenchymal components of MCB and expression levels in epithelial components were variable. The correlation of positive expression of SPARC and poor long-term survival in IDC is significant (p = 0.004). Individuals with positive SPARC expression had 2.34 times higher hazard of death compared with those with negative SPARC expression after adjusting for factors including positive lymph node, TNM tumor stage, estrogen receptor, and progesterone receptor. Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC.

  1. 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

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

    Science.gov (United States)

    Chapa, Joaquin; Bourgo, Ryan J; Greene, Geoffrey L; Kulkarni, Swati; An, Gary

    2013-01-01

    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 augment the

  3. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    Science.gov (United States)

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-03-16

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  4. Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Hawthorn Lesleyann

    2010-08-01

    Full Text Available Abstract Background A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs. This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'. Methods We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs. Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH analysis to identify genes showing altered expression in LOH regions. Results Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples. Conclusion We have demonstrated the utility of the application of

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

    Directory of Open Access Journals (Sweden)

    Srovnal Josef

    2007-03-01

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

  6. Is stage-specific embryonic antigen 4 a marker for human ductal stem/progenitor cells?

    Science.gov (United States)

    Afrikanova, Ivka; Kayali, Ayse; Lopez, Ana; Hayek, Alberto

    2012-08-01

    The presence of pancreatic stem cells (PnSCs) has not been firmly demonstrated in the human or animal pancreas. Previous reports have suggested that ductal and acinar structures in the exocrine pancreas can be a potential source of progenitor cells. More recently, immature insulin precursors in the periphery of human islets have been found to self-replicate and differentiate to endocrine cells in vitro. Transplantation of these cells under the kidney capsule improves the diabetic state in mice. The controversy surrounding where PnSCs reside could be resolved if a specific marker were to be found that allowed their identification, purification, and directed differentiation to endocrine cells. We have identified in human pancreas cells positive for the stage-specific embryonic antigen 4 (SSEA4), a stem cell marker. These cells also express ductal, pancreatic progenitor, and stem cell protein markers. Interestingly, some of the SSEA4(+) cells scattered in the ducts do not show a ductal cell phenotype. SSEA4(+)-sorted cells formed aggregate-like spheres in culture and robustly differentiated to pancreatic hormone-expressing cells in conditions of high glucose concentration and B27 supplementation. We hypothesize that SSEA4(+) cells or a subpopulation of those cells residing in the pancreatic ducts may be the elusive PnSCs, and in this case, SSEA4 may represent a potential surface antigen marker for human PnSCs. The discovery of specific markers for the identification and purification of human PnSCs would greatly facilitate studies aimed at the expansion of these cells and the development of targeting tools for their potential induction to insulin-producing cells.

  7. Is Stage-Specific Embryonic Antigen 4 a Marker for Human Ductal Stem/Progenitor Cells?

    Science.gov (United States)

    Kayali, Ayse; Lopez, Ana; Hayek, Alberto

    2012-01-01

    Abstract The presence of pancreatic stem cells (PnSCs) has not been firmly demonstrated in the human or animal pancreas. Previous reports have suggested that ductal and acinar structures in the exocrine pancreas can be a potential source of progenitor cells. More recently, immature insulin precursors in the periphery of human islets have been found to self-replicate and differentiate to endocrine cells in vitro. Transplantation of these cells under the kidney capsule improves the diabetic state in mice. The controversy surrounding where PnSCs reside could be resolved if a specific marker were to be found that allowed their identification, purification, and directed differentiation to endocrine cells. We have identified in human pancreas cells positive for the stage-specific embryonic antigen 4 (SSEA4), a stem cell marker. These cells also express ductal, pancreatic progenitor, and stem cell protein markers. Interestingly, some of the SSEA4+ cells scattered in the ducts do not show a ductal cell phenotype. SSEA4+-sorted cells formed aggregate-like spheres in culture and robustly differentiated to pancreatic hormone-expressing cells in conditions of high glucose concentration and B27 supplementation. We hypothesize that SSEA4+ cells or a subpopulation of those cells residing in the pancreatic ducts may be the elusive PnSCs, and in this case, SSEA4 may represent a potential surface antigen marker for human PnSCs. The discovery of specific markers for the identification and purification of human PnSCs would greatly facilitate studies aimed at the expansion of these cells and the development of targeting tools for their potential induction to insulin-producing cells. PMID:23515456

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

    OpenAIRE

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

    2015-01-01

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

  9. TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.

    Science.gov (United States)

    Liu, Jun; Akanuma, Naoki; Liu, Chengyang; Naji, Ali; Halff, Glenn A; Washburn, William K; Sun, Luzhe; Wang, Pei

    2016-08-03

    Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-β1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases.

  10. Regressive change in high-grade ductal carcinoma in situ of the breast: histopathologic spectrum and biologic importance.

    Science.gov (United States)

    Wasserman, Jason K; Parra-Herran, Carlos

    2015-09-01

    High-grade ductal carcinoma in situ (HG-DCIS) of the breast often shows tumor attenuation and reactive fibrosis. These changes, previously described as "regressive," have been paradoxically associated with an increased risk of invasive carcinoma. We aimed to further characterize the spectrum of the so-called regressive changes (RCs) in HG-DCIS. We reviewed 52 consecutive cases of HG-DCIS on biopsy specimens followed by excision. RCs were divided into early (stage 1) and advanced (stages 2 and 3) stages according to the degree of ductal fibrosis and tumor effacement. The presence of inflammation, hormone receptor status, and diagnosis on excision were recorded. RCs were seen in 51 (98%) cases: 96%, 76.4%, and 39.2% cases showed stages 1, 2, and 3, respectively. Periductal T cells with a normal CD4/CD8 ratio were constantly seen. Advanced RCs and inflammation were more frequent in estrogen and progesterone receptor-negative tumors. RCs were not associated with invasion but correlated with a larger residual HG-DCIS volume on excision. Regression in HG-DCIS is frequent. It may reflect a targeted immune response to certain phenotypes, mainly hormone receptor-negative lesions. Nonetheless, RCs do not lead to complete tumor obliteration but correlate with aggressive tumor characteristics instead. Copyright© by the American Society for Clinical Pathology.

  11. 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.

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

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    Ya'an Kang

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

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

    OpenAIRE

    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 an...

  14. 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.

  15. Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    A S Rathore

    2013-01-01

    Full Text Available Background: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC of the breast. Materials and Methods: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. Results: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively. The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021. Conclusions: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

  16. [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

    Antecedentes: en pacientes con carcinoma ductal in situ la biopsia de ganglio centinela es motivo de controversia porque se reportan ganglios positivos en 1.4-12.5% debido al carcinoma invasor oculto en la pieza quirúrgica. Objetivo: conocer la frecuencia de metástasis en ganglio centinela en pacientes con carcinoma ductal in situ e identificar las diferencias entre los casos positivos y negativos. Material y métodos: estudio retrospectivo, transversal, analítico de pacientes con carcinoma ductal in situ a quienes se realizó una biopsia de ganglio centinela por requerir mastectomía, tener un tumor palpable, lesión radiológica = 5 cm, inadecuada relación mama-tumor o porque la escisión pudiera afectar el flujo linfático. Resultados: de 168 carcinomas in situ, se incluyeron 50 casos con carcinoma ductal in situ y biopsia de ganglio centinela, de pacientes con edad promedio de 51.6 años, 30 (60%) de ellas asintomáticas. Los signos reportados fueron: nódulo palpable (18%), secreción por el pezón (12%) o ambos (8%). Predominaron las microcalcificaciones (72%), comedonecrosis (62%) y grado histológico -2 (44%) con 28% de receptores hormonales negativos. En el estudio transoperatorio 4 (8%) pacientes tuvieron ganglio centinela positivo y un caso en estudio histopatológico definitivo (60% micrometástasis, 40% macrometástasis), todos con carcinoma invasor en la pieza quirúrgica. Las pacientes con ganglio centinela transoperatorio positivo eran más jóvenes (44.5 vs 51 años), con más tumores palpables (50 vs 23.1%), más grandes (3.5 vs 2 cm), más comedonecrosis (75 vs 60.8%), más indiferenciados (75% vs 39.1%) y menos receptores hormonales (50 vs 73.9%), que las que tenían ganglio centinela negativo, sin que estas diferencias tuvieran significación estadística. Conclusiones: puesto que 1 de cada 12 pacientes con carcinoma ductal in situ tiene afectación ganglionar en el ganglio centinela, se recomienda seguir tomando la biopsia para evitar

  17. Increased Levels of Erythropoietin in Nipple Aspirate Fluid and in Ductal Cells from Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ferdinando Mannello

    2008-01-01

    Full Text Available Background: Erythropoietin (Epo is an important regulator of erythropoiesis, and controls proliferation and differentiation of both erythroid and non-erythroid tissues. Epo is actively synthesized by breast cells during lactation, and also plays a role in breast tissues promoting hypoxia-induced cancer initiation. Our aims are to perform an exploratory investigation on the Epo accumulation in breast secretions from healthy and cancer patients and its localization in breast cancer cells.

  18. High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

    Science.gov (United States)

    Sun, Xian-Fu; Shao, Ying-Bo; Liu, Ming-Ge; Chen, Qi; Liu, Zhao-Jun; Xu, Bin; Luo, Su-Xia; Liu, Hui

    2017-05-01

    Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

  19. Evidence for a stem cell hierarchy in the adult human breast

    DEFF Research Database (Denmark)

    Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone

    2007-01-01

    in situ confirmed this pattern. The proposal that the four cell types are indeed constituents of an as of yet undescribed stem cell hierarchy was assessed in long-term cultures in which senescence was bypassed. These findings identify an adult human breast ductal stem cell activity and its earliest...

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

    DEFF Research Database (Denmark)

    Ponti, Antonio; Lynge, Elsebeth; James, Ted

    2014-01-01

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

  1. Reproductive and menstrual factors and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Kim, Mimi Y; Woods, Nancy F; Habel, Laurel A; Messina, Catherine R; Wactawski-Wende, Jean; Stefanick, Marcia L; Chlebowski, Rowan T; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2011-10-01

    The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood. The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women's Health Initiative (WHI) clinical trial participants, in which mammography was protocol mandated. The cohort consisted of 64,060 women, among whom 664 cases of DCIS were ascertained over a median follow-up of 12.0 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). After adjustment for covariates, only older age at menopause (HR ≥ 55 vs. 45-54 : 1.39, 95% CI 1.08-1.79) was significantly associated with risk; however, greater parity (HR ≥ 5 live births vs. 0: 0.70, 95% CI 0.47-1.03), among parous women, and age at first live birth (HR ≥ 30 years relative to <20 years: 1.32, 95% CI 0.92-1.90) were of borderline significance. Age at menarche and months of breast-feeding were not associated with risk. Associations did not differ between high- and low-/moderate-grade DCIS, or by level of body mass index or family history of breast cancer; however, there was a suggestion that the associations of age at menopause, parity, and age at first live birth were limited to women who had ever used hormone therapy. Findings from this large cohort of postmenopausal women suggest that age at menopause, and possibly, age at first live birth, and parity are associated with risk of DCIS, whereas age at menarche and duration of breast-feeding are not.

  2. 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.

  3. 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.

  4. Lacrimal gland ductal carcinomas

    DEFF Research Database (Denmark)

    Andreasen, Simon; Grauslund, Morten; Heegaard, Steffen

    2017-01-01

    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...

  5. Novel clinical trial designs for treatment of ductal carcinoma in situ of the breast with trastuzumab (herceptin).

    Science.gov (United States)

    Gonzalez, Ricardo J; Buzdar, Aman U; Fraser Symmans, W; Yen, Tina W; Broglio, Kristine R; Lucci, Anthony; Esteva, Francisco J; Yin, Guosheng; Kuerer, Henry M

    2007-01-01

    Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored.

  6. 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.

  7. Alcohol consumption and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Kim, Mimi; Shikany, James M; Rodgers, Allison K; Wactawski-Wende, Jean; Lane, Dorothy; Powell, Lynda; Stefanick, Marcia L; Freiberg, Matthew S; Kazlauskaite, Rasa; Chlebowski, Rowan T; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2010-08-01

    Observational studies have commonly linked higher alcohol consumption with a modest increase in invasive breast cancer risk, but cohort studies have not examined alcohol intake in relation to ductal carcinoma in situ (DCIS). The association between adulthood alcohol consumption assessed at baseline and subsequent DCIS risk was examined in a cohort of postmenopausal women participating in the Women's Health Initiative clinical trials, in which mammography was protocol-mandated. Alcohol intake was assessed by a semiquantitative food-frequency questionnaire. Reported DCIS cases were verified by central pathology report review. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. The cohort consisted of 63,822 women with information on alcohol intake, among whom 489 cases of DCIS were ascertained after a median follow-up of 8.0 years. For the primary analysis, invasive breast cancer was treated as a competing risk, and follow-up time was censored at the date of diagnosis of invasive breast cancer. After adjustment for covariates, the hazard ratio for DCIS among women who consumed 14 or more servings of alcohol per week, relative to nondrinkers, was 0.87 (95% confidence interval, 0.50-1.51). In addition, alcohol intake was not associated with risk of either high-grade or low-/moderate-grade DCIS. In this large cohort study of postmenopausal women, alcohol consumption was not associated with risk of DCIS. If other studies confirm our findings, this would suggest that alcohol may have an effect later in the carcinogenic process. (c)2010 AACR.

  8. Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Fuh Yong, E-mail: fuhyong@yahoo.com [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Wang, Fuqiang [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Chen, John Ju [Department of Cancer Informatics, National Cancer Centre Singapore (Singapore); Tan, Chiew Har [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); Tan, Puay Hoon [Department of Pathology, Singapore General Hospital (Singapore)

    2014-04-01

    Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.

  9. 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scan Findings for Ductal Carcinomas of Breast: Association of Standardized Uptake Value and Histological Findings

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-15

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

  10. Aluminium and the human breast.

    Science.gov (United States)

    Darbre, P D

    2016-06-01

    The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of the breast: correlation with prognosis and the cancer-stromal interaction.

    Directory of Open Access Journals (Sweden)

    Akemi Morikawa

    Full Text Available We examined the pathobiological properties of beclin-1, which is a key regulator of autophagosome formation in invasive ductal carcinoma of the breast, with a particular focus on the cancer microenvironment. Immunohistochemistry demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1 in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1 in cancer or stromal cells alone did not correlate with patient prognosis. In contrast, loss of beclin-1 in cancer cells and overexpression in stromal mesenchymal cells was associated with local cancer recurrence, postoperative lymph node metastasis, and a poor disease-free survival rate. A comprehensive gene expression analysis was performed on a co-culture of breast cancer cells and mesenchymal stromal cells, that latter of which either expressed beclin-1 or was depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1 in mesenchymal cells co-cultured with breast cancer cells decreased the levels of various pro-inflammatory cytokines, their receptors, and collagen receptors. Quantitative reverse transcription polymerase chain reaction analysis confirmed that reduction of stromal beclin-1 expression decreased the expression of IL-1β and collagen receptor discoidin domain receptor 2 (DDR2. Microenvironmental IL-1β is believed to play an important role in tumor invasion. Recent work has also indicated that overexpression of DDR2 contributes to breast cancer invasion and lymph node metastasis. Taken together, these findings indicate beclin-1 expression in the stroma might be important for shaping the breast cancer microenvironment and thus could be a potent molecular target in patients with invasive ductal carcinoma of the breast.

  12. Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Berkman, Amy; F Cole, Bernard; Ades, Philips A; Dickey, Samantha; Higgins, Stephen T; Trentham-Dietz, Amy; Sprague, Brian L; Lakoski, Susan G

    2014-11-01

    Ductal carcinoma in situ (DCIS) of the breast represents 15-20% of new breast cancer diagnoses in the US annually. However, long-term competing risks of mortality, as well as racial differences in outcomes among US women with DCIS, are unknown. Case data from the years 1978-2010 were obtained using SEER*Stat software available through the National Cancer Institute from the 2010 SEER registries. Included were all women aged 40 and over with newly diagnosed DCIS. There were 67,514 women in the analysis, including 54,518 white women and 6,113 black women. A total of 12,173 deaths were observed over 607,287 person-years of follow-up. The 20-year cumulative incidence of all-cause death among women with DCIS was 39.6% (CI 38.9-40.3). The corresponding 20-year rates for breast cancer death and CVD death were 3.2% (CI 3.0-3.4) and 13.2% (CI 12.8-13.7), respectively. Black women with DCIS had a higher risk of death compared to white women, with these hazard ratios elevated throughout the entire study period. For example, between 1990 and 2010, black women had a higher risk of all-cause death (HR 3.06, CI 2.39-3.91), breast cancer death (HR 5.78, CI 3.16-10.57), and CVD death (HR 6.43, CI 3.61-11.45) compared to white women diagnosed between 50 and 59 years of age. The risk of all-cause and CVD death was greater than breast cancer death among women diagnosed with DCIS over 20 years. Black women had higher risks of dying from all-causes compared to white women. These differences persisted into the modern treatment era.

  13. The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas

    Directory of Open Access Journals (Sweden)

    Li-Yun Chang

    2015-01-01

    Full Text Available Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(− and ER(−/ER(+ mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(− breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature.

  14. 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.

  15. Grading ductal carcinoma in situ of the breast using an automated proliferation index.

    Science.gov (United States)

    Stasik, Christopher J; Davis, Marilyn; Kimler, Bruce F; Fan, Fang; Damjanov, Ivan; Thomas, Patricia; Tawfik, Ossama W

    2011-01-01

    Tumor grade, size and margin status are the most significant factors in predicting the behavior of ductal carcinoma in-situ (DCIS). The inclusion of necrosis and nuclear grade in the grading of DCIS has demonstrated a fair but suboptimal agreement between pathologists. The grading of DCIS was studied and compared to the Van Nuys (VN) system, by using our newly proposed unifying "nuclear grade + proliferation index (N+P) grading system for invasive carcinomas. 162 DCIS tumors were studied including 49 VN I, 31 VN II, and 82 VN III cases. The VN and N+P systems were compared with each other and correlated with tumor size, ER, PR, p53, Her-2, EGFR, Bcl-2, p27 and p21 status. The two systems demonstrated similar frequencies for the different grades and an agreement with each other for all of the biomarkers studied. The greatest difference between the two systems was observed for those tumors initially classified as VN II (94% being down-graded to N+P I) and VN III (80% being down-graded to N+P II). These results suggest that the N+P system, combining nuclear grade with automated MIB-1 count, is a potentially valid and reproducible grading system for both non-invasive and invasive mammary carcinomas. It is automated, less subjective in assessing mitotic activity and necrosis and correlates with other prognostic biomarkers.

  16. Correlation between imaging and pathology in ductal carcinoma in situ of the breast

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    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.

  17. Aberrant methylation of Glutathione S-transferase P1 and E-cadherin in invasive ductal breast carcinoma and fibroadenoma

    Institute of Scientific and Technical Information of China (English)

    Wings Tjing Yung Loo; Mary Ngan Bing Cheung; Louis Wing Cheong Chow

    2010-01-01

    Objective To investigate the hypermethylation status of glutathione transferase P1(GSTP1) and E cadherin (ECAD), TSGs (tumor suppressor genes) in our breast cancer samples and explore their correlation with clinicopathological features of corresponding cancer patients. Methods One hundred and thirty six IDC (invasive ductal carcinoma) patients were recruited for analysis and 16 fibroadenoma patients acted as control. DNA extraction and methylation specific PCR (MSP) were subsequently performed preceded by pathological examination. Results The percentage of hypermethylated GSTP1 in carcinoma and fibroadenoma groups was 34.92% and 15.79% respectively and the percentage of hypermethylated ECAD in carcinomas and fibroadenomas was 18.00% and 0.00% respectively. Carcinoma had the highest percentage of c erbB2 overexpression being 54.55% among the clinicopathological parameters. Conclusion Hypermethylation patterns are frequent in IDC and seem to relate to c erbB2 overexpression, and such epigenetic change should not be neglected in fibroadenoma. Tumor methylation status in cancer patients can be determined at early stage and it may be a reference for better treatment planning.

  18. 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

  19. HIF-1alpha and NOTCH signaling in ductal and lobular carcinomas of the breast

    NARCIS (Netherlands)

    Ercan, C.; Vermeulen, J.F.; Hoefnagel, L.; Bult, P.; Groep, P. van der; Wall, E. van der; Diest, P.J. van

    2012-01-01

    BACKGROUND: NOTCH signaling is involved in every step of metazoan development and maintenance of adult tissue homeostasis. It is frequently deregulated by mutations and overexpression in different cancer types including solid tumors such as breast cancer. Another common feature of solid tumors is hy

  20. Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.

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    Sullu, Yurdanur; Demirag, Guzin G; Yildirim, Arzu; Karagoz, Filiz; Kandemir, Bedri

    2011-12-15

    Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

  1. 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.

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    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.

  2. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

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    Magers, Martin J; Dueber, Julie C; Lew, Madelyn; Pang, Judy C; Davenport, Robertson D

    2016-06-01

    Metastases to the thyroid are uncommon [thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

  3. Neurotensin is a Versatile Modulator of In Vitro Human Pancreatic Ductal Adenocarcinoma Cell (PDAC Migration

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    Tatjana Mijatovic

    2007-01-01

    Full Text Available Background: While the neurotensin (NT roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described. Methods: The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays. Results: The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of αV and β5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway. Conclusion: This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.

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

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    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.

  5. Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling.

    Science.gov (United States)

    Hohwieler, Meike; Illing, Anett; Hermann, Patrick C; Mayer, Tobias; Stockmann, Marianne; Perkhofer, Lukas; Eiseler, Tim; Antony, Justin S; Müller, Martin; Renz, Susanne; Kuo, Chao-Chung; Lin, Qiong; Sendler, Matthias; Breunig, Markus; Kleiderman, Susanne M; Lechel, André; Zenker, Martin; Leichsenring, Michael; Rosendahl, Jonas; Zenke, Martin; Sainz, Bruno; Mayerle, Julia; Costa, Ivan G; Seufferlein, Thomas; Kormann, Michael; Wagner, Martin; Liebau, Stefan; Kleger, Alexander

    2017-03-01

    The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish. Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas without evidence of tumour formation or transformation. Finally, we implemented this unique phenotyping tool as a model to study the pancreatic facets of cystic fibrosis (CF). For the first time, we provide evidence that in vitro, but also in our xenograft transplantation assay, pancreatic commitment occurs generally unhindered in CF. Importantly, cystic fibrosis transmembrane conductance regulator (CFTR) activation in mutated pancreatic organoids not only mirrors the CF phenotype in functional assays but also at a global expression level. We also conducted a scalable proof-of-concept screen in CF pancreatic organoids using a set of CFTR correctors and activators, and established an mRNA-mediated gene therapy approach in CF organoids. Taken together, our platform provides novel opportunities to model pancreatic disease and development, screen for disease-rescuing agents and to test therapeutic procedures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. 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

    2008-05-01

    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.

  7. Fine-needle aspiration of gray zone lesions of the breast: fibroadenoma versus ductal carcinoma.

    Science.gov (United States)

    Jing, Xin; Normolle, Daniel; Michael, Claire W

    2013-09-01

    While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology-confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re-classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a

  8. Eliminating "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) terminology in clinical breast practice: The cognitive psychology point of view.

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    Pravettoni, Gabriella; Yoder, Whitney R; Riva, Silvia; Mazzocco, Ketti; Arnaboldi, Paola; Galimberti, Viviana

    2016-02-01

    There is evidence from the literature that the terms "ductal carcinoma in situ" and "lobular carcinoma in situ" (DCIS and LCIS) should be eliminated in clinical breast cancer practice and replaced with the new "ductal intraepithelial neoplasia" (DIN) and "lobular intraepithelial neoplasia" (LIN) terminology. The main purpose of the present article is to expand on this argument from a cognitive psychology perspective and offer suggestions for further research, emphasizing how the elimination of the term "carcinoma" in "in situ" breast cancer diagnoses has the potential to reduce both patient and health care professional confusion and misperceptions that are often associated with the DCIS and LCIS diagnoses, as well as limit the adverse psychological effects of women receiving a DCIS or LCIS diagnosis. We comment on the recent peer-reviewed literature on the clinical implications and psychological consequences for breast cancer patients receiving a DCIS or LCIS diagnosis and we use a cognitive perspective to offer new insight into the benefits of embracing the new DIN and LIN terminology. Using cognitive psychology and cognitive science in general, as a foundation, further research is advocated in order to yield data in support of changing the terminology and therefore, offer a chance to significantly improve the lives and psychological sequelae of women facing such a diagnosis. Typology: Controversies/Short Commentary.

  9. Ductal Carcinoma In Situ of the Breast: Evaluating the Role of Radiation Therapy in the Management and Attempts to Identify Low-risk Patients.

    Science.gov (United States)

    Shah, Chirag; Vicini, Frank A; Berry, Sameer; Julian, Thomas B; Wilkinson, John Ben; Shaitelman, Simona F; Khan, Atif; Finkelstein, Steven E; Goldstein, Neal

    2015-10-01

    Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected "low-risk" patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.

  10. Myoepithelial cells from pleomorphic adenoma are not influenced by tumor conditioned media from breast ductal adenocarcinoma and melanoma cells: An in vitro study.

    Science.gov (United States)

    Martinez, Elizabeth Ferreira; Demasi, Ana Paula Dias; Napimoga, Marcelo Henrique; Silva, Carolina Amália Barcellos; Navarini, Natalia Festugatto; Araújo, Ney Soares; DE Araújo, Vera Cavalcanti

    2015-01-01

    Myoepithelial cells have been implicated in the regulation of the transition from in situ to invasive neoplasia in salivary gland tumors. Considering the importance of the microenvironment of the tumor, the present in vitro study therefore analyzed the morphological and phenotypic changes undergone by benign myoepithelial cells from pleomorphic adenoma (PA) stimulated by tumor-conditioned medium. The benign myoepithelial cells were obtained from PA and were cultured with fibronectin extracellular matrix protein, supplemented with tumor-conditioned medium, which was harvested from breast ductal adenocarcinoma AU-565 and melanoma Hs 852.T cells. The morphological alterations were assessed by immunofluorescence analysis using vimentin antibody. The α-smooth muscle actin (α-SMA) and fibroblast growth factor (FGF)-2 proteins were analyzed by indirect immunofluorescence and quantitative polymerase chain reaction (qPCR). No morphological changes were observed in the myoepithelial cells cultured in fibronectin protein under stimulation from either tumor-conditioned medium. The immunofluorescence results, which were supported by qPCR analysis, revealed that only α-SMA was upregulated in the fibronectin substratum, with or without tumor-conditioned medium obtained from breast ductal adenocarcinoma and melanoma cells. No significant difference in FGF-2 mRNA expression was detected when the cells were cultured either in the tumor-conditioned medium or in the fibronectin substratum. The tumor-conditioned medium harvested from breast ductal adenocarcinoma and melanoma did not affect myoepithelial cell differentiation and function, which was reflected by the fact that there was no observed increase in α-SMA and FGF-2 expression, respectively.

  11. CA15.3 Serum Concentrations in Older Women with Infiltrating Ductal Carcinomas of the Breast

    Directory of Open Access Journals (Sweden)

    Álvaro Ruibal

    2014-10-01

    Full Text Available Breast cancer is currently becoming a disease of the elderly. We have studied the relation between CA 15.3 serum concentrations and clinical-pathological parameters in 69 women with IDC aged over 70 years (76.3 ± 4.2; range: 71–88; median 76. A group of 205 women with the same tumor but aged <70 years (62.8 ± 4.0; range: 55–70; median 63 was also considered for comparison. Tumor size, axillary lymph node involvement, distant metastasis and histological grade were taken account. Serum CA 15.3 was determined by luminescence assay. CA 15.3 serum concentrations ranged between 6 and 85 U/mL (median 22.9 U/mL, and were higher only in patients with greater (qualitative and quantitative; p: 0.041 tumor size. Our results show that in women with IDCs, and aged over 70 years, serum CA 15.3 serum concentrations are associated exclusively with a greater tumor size, being these findings different to those described in women with the same subtype of tumor considered as a whole or with lower age.

  12. Aluminium and human breast diseases.

    Science.gov (United States)

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

  13. 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.

  14. 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

    2015-04-01

    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.

  15. Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ: relationships with markers of tumor hypoxia and microvascularity.

    Science.gov (United States)

    Currie, Margaret J; Beardsley, Brooke E; Harris, Gavin C; Gunningham, Sarah P; Dachs, Gabi U; Dijkstra, Birgit; Morrin, Helen R; Wells, J Elisabeth; Robinson, Bridget A

    2013-03-01

    We performed immunohistochemical analysis of 3 cancer stem cell-related markers (CD44(+)/CD24(-/low), aldehyde dehydrogenase [ALDH]-1, CD133) in 94 invasive ductal carcinomas and assessed relationships with markers of hypoxia (carbonic anhydrase IX [CAIX]), tumor microvessel density (CD31), and clinicopathologic variables. Overall, 10% of tumors were CD44(+)/CD24(-/low), 13% were ALDH-1(+), 25% were CD133(+), 35% were immunonegative, and 1 tumor was immunopositive for all 3 markers. Associated ductal carcinoma in situ (DCIS) was present in 48% of tumors. Marker immunopositivity was detected in DCIS in 13% (CD44(+)/CD24(-/low)), 7% (ALDH-1(+)), and 32% (CD133(+)) of these tumors and was more likely present in DCIS when also detected in the invasive compartment (P = .03, P = .001, and P = .009, respectively). CD44(+)/CD24(-/low) cells were more common in progesterone receptor-negative tumors (P breast cancers (P breast cancer and showed that CD44(+)/CD24(-/low) and CD133(+) cells were more frequently observed in hypoxic regions of tumor, whereas ALDH-1(+) cells more commonly colocalized to tumors with high microvessel density.

  16. 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

    Science.gov (United States)

    Barajas-Castañeda, Luis Miguel; Cortés-Gutiérrez, Evelin; García-Rodríguez, Francisco Mario; Campos-Rodríguez, Rafael; Lara-Padilla, Eleazar; Enríquez-Rincón, Fernando; Figueroa-Arredondo, Paula

    2016-01-01

    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. PMID:27975070

  17. 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.

  18. Long-Term Outcome in Patients With Ductal Carcinoma In Situ Treated With Breast-Conserving Therapy: Implications for Optimal Follow-up Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Shaitelman, Simona F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wilkinson, J. Ben [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Kestin, Larry L. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ye Hong [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Goldstein, Neal S. [Advanced Diagnostics Laboratory, Redford, Michigan (United States); Martinez, Alvaro A. [Michigan HealthCare Professionals, Pontiac, Michigan (United States); Vicini, Frank A., E-mail: fvicini@pol.net [Michigan HealthCare Professionals, Pontiac, Michigan (United States)

    2012-07-01

    Purpose: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT). Methods and Materials: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. Results: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points. Conclusions: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

  19. 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.

  20. In vitro cultivation of human fetal pancreatic ductal stem cells and their differentiation into insulin-producing cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Xiang Yao; Mao-Lin Qin; Jian-Jun Liu; Xing-Shu Chen; De-Shan Zhou

    2004-01-01

    AIM: To isolate, culture and identify the human fetal pancreatic ductal stem cells in vitro, and to observe the potency of these multipotential cells differentiation into insulin-producing cells.METHODS: The human fetal pancreas was digested by 1 g/L collagease type Ⅳ and then 2.5 g/L trypsin was used to isolate the pancreatic ducta stem cells, followed by culture in serum-free, glucose-free DMEM media with some additional chemical substrates in vitro (according to the different Stage). The cells were induced by glucose-free (control),5 mmol/L, 17.8 mmol/L and 25 mmol/L glucose, respectively.The cell types of differentiated cells were identified using immunocytochemical staining.RESULTS: The shape of human fetal pancreatic ductal stem cells culturedin vitro was firstly fusiform in the first 2 wk,and became monolayer and cobblestone pattern after another 3 to 4 wk. After induced and differentiated by the glucose of different concentrations for another 1 to 2 wk,the cells formed the pancreatic islet-like structures. The identification and potency of these cells were then identified by using the pancreatic ductal stem cell marker, cytokeratin-19 (CK-19), pancreatic β cell marker, insulin and pancreatic α cell marker, glucagons with immunocytochemical staining.At the end of the second week, 95.2% of the cells were positive for CK-19 immunoreactivity. Up to 22.7% of the cells induced by glucose were positive for insulin immunoreactivity, and less than 3.8% of the cells were positive for glucagon immunoreactivity in pancreatic isletlike structures. The positive ratio of immunoreactive staining was dependent on the concentration of glucose, and it was observed that the 17.8 mmol/L glucose stimulated effectively to produce insulin- and glucagons-producing cells.CONCLUSION: The human fetal pancreatic ductal stem cells are capable of proliferation in vitro. These cells have multidifferentiation potential and can be induced by glucose and differentiated into insulin

  1. 乳腺导管原位癌发病率、治疗和预后的系统评价%Ductal Carcinoma in Situ of the Breast: A Systematic Review of Incidence, Treatment, and Outcomes

    Institute of Scientific and Technical Information of China (English)

    王颀; 连臻强; 郭子柏

    2011-01-01

    @@ 1 文献来源 Virnig BA, Tuttle TM, Shamliyan T, et al.Ductal carcinoma in situ of the breast: A systematic review of incidence, treatment, and outcomes[J].J Natl Cancer Inst, 2010, 102 (3) : 170-178.

  2. GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast.

    Science.gov (United States)

    Scaling, Allison L; Prossnitz, Eric R; Hathaway, Helen J

    2014-06-01

    17β-Estradiol (estrogen), through receptor binding and activation, is required for mammary gland development. Estrogen stimulates epithelial proliferation in the mammary gland, promoting ductal elongation and morphogenesis. In addition to a developmental role, estrogen promotes proliferation in tumorigenic settings, particularly breast cancer. The proliferative effects of estrogen in the normal breast and breast tumors are attributed to estrogen receptor α. Although in vitro studies have demonstrated that the G protein-coupled estrogen receptor (GPER, previously called GPR30) can modulate proliferation in breast cancer cells both positively and negatively depending on cellular context, its role in proliferation in the intact normal or malignant breast remains unclear. Estrogen-induced GPER-dependent proliferation was assessed in the immortalized nontumorigenic human breast epithelial cell line, MCF10A, and an ex vivo organ culture model employing human breast tissue from reduction mammoplasty or tumor resections. Stimulation by estrogen and the GPER-selective agonist G-1 increased the mitotic index in MCF10A cells and proportion of cells in the cell cycle in human breast and breast cancer explants, suggesting increased proliferation. Inhibition of candidate signaling pathways that may link GPER activation to proliferation revealed a dependence on Src, epidermal growth factor receptor transactivation by heparin-bound EGF and subsequent ERK phosphorylation. Proliferation was not dependent on matrix metalloproteinase cleavage of membrane-bound pro-HB-EGF. The contribution of GPER to estrogen-induced proliferation in MCF10A cells and breast tissue was confirmed by the ability of GPER-selective antagonist G36 to abrogate estrogen- and G-1-induced proliferation, and the ability of siRNA knockdown of GPER to reduce estrogen- and G-1-induced proliferation in MCF10A cells. This is the first study to demonstrate GPER-dependent proliferation in primary normal and malignant

  3. Invasive ductal carcinomas of the breast showing partial reversed cell polarity are associated with lymphatic tumor spread and may represent part of a spectrum of invasive micropapillary carcinoma.

    Science.gov (United States)

    Acs, Geza; Esposito, Nicole N; Rakosy, Zsuzsa; Laronga, Christine; Zhang, Paul J

    2010-11-01

    Invasive micropapillary carcinomas (IMPC) of the breast are aggressive tumors frequently associated with lymphatic invasion and nodal metastasis even when micropapillary (MP) differentiation is very focal within the tumors. We have noticed that some breast carcinomas showing lymphatic spread but lacking histologic features of IMPC have occasional tumor cell clusters reminiscent of those of IMPC without the characteristic prominent retraction artifact. To study the clinicopathologic significance of such features, we prospectively selected 1323 invasive ductal carcinomas and determined the presence and extent of MP differentiation and retraction artifact in the tumors. One representative tumor block per case was used for immunostaining for epithelial membrane antigen (EMA). Partial reverse cell polarity (PRCP) was defined as prominent linear EMA reactivity on at least part of the periphery of tumor cell clusters usually associated with decreased cytoplasmic staining. The clinicopathologic features of carcinomas with PRCP were compared with IMPC and invasive ductal (no special type) carcinomas without this feature. Of the 1323 cases, 96 (7.3%) and 92 (7.0%) showed MP features and the presence of PRCP, respectively. We found that the presence of both PRCP and MP features were strongly associated with decreased cytoplasmic EMA immunoreactivity and the presence of lymphatic invasion and nodal metastasis, even if such features were present only very focally. Our results suggest that breast carcinomas with PRCP may have the same implication as MP differentiation and these tumors may represent part of a spectrum of IMPC. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.

  4. Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

    Energy Technology Data Exchange (ETDEWEB)

    Lalani, Nafisha; Paszat, Lawrence [University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Sutradhar, Rinku; Thiruchelvam, Deva [Institute for Clinical Evaluative Sciences, Toronto, Ontario (Canada); Nofech-Mozes, Sharon; Hanna, Wedad; Slodkowska, Elzbieta [University of Toronto, Toronto, Ontario (Canada); Department of Anatomic Pathology, Sunnybrook Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Done, Susan J. [University of Toronto, Toronto, Ontario (Canada); Laboratory Medicine Program, University Health Network and Department of Laboratory Medicine and Pathobiology, Campbell Family Institute for Breast Cancer Research, Toronto, Ontario (Canada); Miller, Naomi; Youngson, Bruce [University of Toronto, Toronto, Ontario (Canada); Laboratory Medicine Program, University Health Network and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Tuck, Alan [Pathology and Laboratory Medicine, London Health Sciences Centre and Saint Joseph' s Health Care, London, Ontario (Canada); Sengupta, Sandip [Department of Pathology and Molecular Medicine, Kingston General Hospital, Kingston, Ontario (Canada); Elavathil, Leela [Department of Anatomical Pathology, Juravinski Hospital, Hamilton Health Sciences, Hamilton, Ontario (Canada); Chang, Martin C. [Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and Department of Laboratory Medicine and Pathobiology, Toronto, Ontario (Canada); Jani, Prashant A. [Department of Anatomical Pathology, Thunder Bay Regional Health Sciences Centre, Thunder Bay, Ontario (Canada); Bonin, Michel [Pathology and Laboratory Medicine, Sudbury Regional Hospital, Sudbury, Ontario (Canada); and others

    2014-12-01

    Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databases and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF regimens

  5. Polyamines in Human Breast Milk

    OpenAIRE

    Nihal Büyükuslu

    2015-01-01

    Human milk is the ideal food for all newborns and infants. It involves macro nutrients and functional compounds for growth and development. The composition of breast milk differs between preterm and term milk. Polyamines are essential for cell proliferation and differentiation. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as food, and intestinal microbiota. Breast milk is the first source of exogenous polyamines...

  6. Hypofractionation and concomitant boost to deliver adjuvant whole-breast radiation in ductal carcinoma in situ (DCIS): a subgroup analysis of a prospective case series.

    Science.gov (United States)

    Cante, Domenico; Franco, Pierfrancesco; Sciacero, Piera; Girelli, Giuseppe; Marra, Anna Maria; Pasquino, Massimo; Russo, Giuliana; Casanova Borca, Valeria; Mondini, Guido; Paino, Ovidio; Numico, Gianmauro; Tofani, Santi; La Porta, Maria Rosa; Ricardi, Umberto

    2014-02-01

    To report the four-year outcomes of accelerated hypofractionated whole-breast radiotherapy (WBRT) with a concomitant boost (CB) to the tumor bed in ductal carcinoma in situ (DCIS), we performed a subgroup analysis of 103 patients affected with DCIS within a cohort of 960 early breast cancer patients treated with breast conservation and hypofractionated WBRT. Prescription dose to the whole breast was 45 Gy (2.25 Gy/20 fractions) with an additional daily CB of 0.25 Gy to the surgical cavity (2.5 Gy/20 fractions up to 50 Gy). With a median follow-up of 48 months (range 12-91), no local recurrence was observed. Maximum detected acute skin toxicity was as follows: G0 in 35 % of patients, G1 in 54 %, G2 in 9 % and G3 in 2 %. Late skin and subcutaneous toxicity were generally mild with only 1 % of patients experiencing ≥G3 events (telangiectasia). No major lung and heart toxicity were detected. Cosmetic results were excellent in 50 % of patients, good in 37 %, fair in 9 % and poor in 4 %. Quality of life had a generally favorable profile both within the functioning and symptoms domains. The present result supports the hypothesis that DCIS patients could be safely treated with a hypofractionated schedule employing a CB to the lumpectomy cavity.

  7. 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.

  8. Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI).

    Science.gov (United States)

    Han, Yang; Wang, Shutao; Hibshoosh, Hanina; Taback, Bret; Konofagou, Elisa

    2016-05-09

    High-intensity focused ultrasound (HIFU) is a noninvasive technique used in the treatment of early-stage breast cancer and benign tumors. To facilitate its translation to the clinic, there is a need for a simple, cost-effective device that can reliably monitor HIFU treatment. We have developed harmonic motion imaging (HMI), which can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely harmonic motion imaging for focused ultrasound (HMIFU). The overall objective of this study was to develop an all ultrasound-based system for real-time imaging and ablation monitoring in the human breast in vivo. HMI was performed in 36 specimens (19 normal, 15 invasive ductal carcinomas, and 2 fibroadenomas) immediately after surgical removal. The specimens were securely embedded in a tissue-mimicking agar gel matrix and submerged in degassed phosphate-buffered saline to mimic in vivo environment. The HMI setup consisted of a HIFU transducer confocally aligned with an imaging transducer to induce an oscillatory radiation force and estimate the resulting displacement. 3D HMI displacement maps were reconstructed to represent the relative tissue stiffness in 3D. The average peak-to-peak displacement was found to be significantly different (p = 0.003) between normal breast tissue and invasive ductal carcinoma. There were also significant differences before and after HMIFU ablation in both the normal (53.84 % decrease) and invasive ductal carcinoma (44.69 % decrease) specimens. HMI can be used to map and differentiate relative stiffness in postsurgical normal and pathological breast tissues. HMIFU can also successfully monitor thermal ablations in normal and pathological human breast specimens. This HMI technique may lead to a new clinical tool for breast tumor imaging and HIFU treatment monitoring.

  9. FT-Raman spectroscopy study of human breast tissue

    Science.gov (United States)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

  10. 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

  11. Effect of radiotherapy on survival of women with locally excised ductal carcinoma in situ of the breast: a Surveillance, Epidemiology, and End Results population-based analysis

    Directory of Open Access Journals (Sweden)

    Qian GW

    2015-06-01

    Full Text Available Guo-Wei Qian,1,* Xiao-Jian Ni,1,* Zheng Wang,2 Yi-Zhou Jiang,1 Ke-Da Yu,1 Zhi-Ming Shao1 1Department of Breast Surgery, 2Department of Radiation Oncology, Shanghai Cancer Center and Cancer Institute, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Although it has been previously reported that radiotherapy (RT effectively reduced the incidence of local recurrence of ductal carcinoma in situ (DCIS following breast-conserving surgery (BCS, little is known about the effect of RT on survival of patients with locally excised DCIS. Patients and methods: Using Surveillance, Epidemiology, and End Results registry data, we selected 56,968 female DCIS patients treated with BCS between 1998 and 2007. Overall survival (OS and breast cancer-specific survival (BCSS were compared among patients who received RT or no RT using the Kaplan–Meier methods and Cox proportional hazards regression models. Results: Median follow-up was 91 months. In the multivariable model, patients receiving postoperative RT had better OS than those undergoing BCS alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.53–0.67, P<0.001. This pattern remained after stratification by estrogen receptor (ER status and age. In contrast, RT delivery was not significantly associated with improved BCSS (HR 0.71, 95% CI 0.48–1.03, P=0.073. However, after stratifying by the above two variables, RT contributed to better BCSS in ER-negative/borderline patients (HR 0.41, 95% CI 0.19–0.88, P=0.023 and younger patients (≤50 years old; HR 0.37, 95% CI 0.15–0.91, P=0.030. Conclusion: Our analysis confirms the beneficial effect of RT on OS in women with locally excised DCIS and reveals the specific protective effect of RT on BCSS in ER-negative/borderline and younger patients. Keywords: ductal carcinoma in situ, breast cancer, breast-conserving surgery, radiotherapy, survival

  12. A Comparison of the Proteomic Expression in Pooled Saliva Specimens from Individuals Diagnosed with Ductal Carcinoma of the Breast with and without Lymph Node Involvement

    Directory of Open Access Journals (Sweden)

    Charles F. Streckfus

    2009-01-01

    Full Text Available Purpose. The objective was to compare the salivary protein profiles of saliva specimens from individuals diagnosed with invasive ductal carcinoma of the breast (IDC with and without lymph node involvement. Methods. Three pooled saliva specimens from women were analyzed. One pooled specimen was from healthy women; another was from women diagnosed with Stage IIa IDC and a specimen from women diagnosed with Stage IIb. The pooled samples were trypsinized and the peptide digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of the digests were combined and analyzed by reverse phase capillary chromatography on an LC-MS/MS mass spectrometer. Results. The results yielded approximately 174 differentially expressed proteins in the saliva specimens. There were 55 proteins that were common to both cancer stages in comparison to each other and healthy controls while there were 20 proteins unique to Stage IIa and 28 proteins that were unique to Stage IIb.

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Mariko; Yuen, Sachiko; Akazawa, Kentaro; Nishida, Kaori; Yamada, Kei [Kyoto Prefectural University of Medicine, Departments of Radiology, Graduate School of Medical Science, Kyoto (Japan); Konishi, Eiichi [Kyoto Prefectural University of Medicine, Departments of Pathology, Graduate School of Medical Science, Kyoto (Japan); Kajihara, Mariko [Kyoto Breast Center Sawai Memorial Clinic, Departments of Radiology, Kyoto (Japan); Shinkura, Nobuhiko [Kyoto Breast Center Sawai Memorial Clinic, Departments of Surgery, Kyoto (Japan)

    2012-06-15

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

  15. SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening

    Energy Technology Data Exchange (ETDEWEB)

    Emdin, Stefan O.; Granstrand, Bengt [Umeaa Univ. Hospital (Sweden). Dept. of Surgery; Ringberg, Anita [Malmoe Univ. Hospital (Sweden). Dept. of Plastic and Reconstructive Surgery; Sandelin, Kerstin [Karolinska Univ. Hospital, Stockholm (Sweden); Arnesson, Lars-Gunnar [Linkoeping Univ. Hospital (Sweden). Dept. of Surgery; Nordgren, Hans [Uppsala Univ. Hospital (Sweden). CLM; Anderson, Harald [Univ. Hospital, Lund (Sweden). Dept. of Cancer Epidemiology; Garmo, Hans; Holmberg, Lars [Uppsala Univ. (Sweden). Regional Oncologic Centre; Wallgren, Arne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Oncology

    2006-07-15

    We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1,046 operated women to postoperative RT or control between 1987 and 1999. The primary endpoint was ipsilateral local recurrence. Secondary endpoints were contralateral breast cancer, distant metastasis and death. After a median follow-up of 5.2 years (range 0.1-13.8) there were 44 recurrences in the RT group corresponding to a cumulative incidence of 0.07 (95% confidence interval (CI) 0.05-0.10). In the control group there were 117 recurrences giving a cumulative incidence of 0.22 (95% CI 0.18-0.26) giving an overall hazard ratio of 0.33 (95% CI 0.24-0.47, p<0.0001). Twenty two percent of the patients had microscopically unknown or involved margins. We found no evidence for different effects of RT on the relative risk of invasive or in situ recurrence. Secondary endpoints did not differ. Women undergoing sector resection for DCIS under conditions of population based screening mammography benefit from postoperative RT to the breast. Seven patients needed RT-treatment to prevent one recurrence.

  16. Protein expression and methylation of MGMT, a DNA repair gene and their correlation with clinicopathological parameters in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Asiaf, Asia; Ahmad, Shiekh Tanveer; Malik, Ajaz Ahmad; Aziz, Shiekh Aejaz; Rasool, Zubaida; Masood, Akbar; Zargar, Mohammad Afzal

    2015-08-01

    Epigenetic mechanisms such as DNA methylation are being increasingly recognized to play an important role in cancer and may serve as a cancer biomarker. The aim of this study was to evaluate the promoter methylation status of MGMT (O6-methylguanine-DNA methyltransferase) and a possible correlation with the expression of MGMT and standard clinicopathological parameters in invasive ductal breast carcinoma patients (IDC) of Kashmir. Methylation-specific PCR was carried out to investigate the promoter methylation status of MGMT in breast tumors paired with the corresponding normal tissue samples from 128 breast cancer patients. The effect of promoter methylation on protein expression in the primary breast cancer and adjacent normal tissues was evaluated by immunohistochemistry (n = 128) and western blotting (n = 30). The frequency of tumor hypermethylation was 39.8 % and a significant difference in methylation frequency among breast tumors were found (p MGMT in 68/128 (53.1 %) tumors. MGMT promoter methylation mediated gene silencing was associated with loss of its protein expression (rs = -0.285, p = 0.001, OR = 3.38, 95 % CI = 1.59-7.17). A significant correlation was seen between loss of MGMT and lymph node involvement (p = 0.030), tumor grade (p MGMT methylation was found to be associated with tumor grade (p = 0.011), tumor stage (p = 0.009), and loss of ER (p = 0.003) and PR receptors (p = 0.009). To our knowledge, our findings, for the first time, in Kashmiri population, indicate that MGMT is aberrantly methylated in breast cancer and promoter hypermethylation could be attributed to silencing of MGMT gene expression in breast cancer. Our data suggests that MGMT promoter hypermethylation could have a potential function as molecular biomarker of breast oncogenesis. Also, based on their predictive value of response to therapy, the immunohistochemical evaluation and interpretation of MGMT may also help in future to

  17. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wendy K Glenn

    Full Text Available BACKGROUND: The purpose of this investigation is to determine if Epstein Barr virus (EBV, high risk human papillomavirus (HPV, and mouse mammary tumour viruses (MMTV co-exist in some breast cancers. MATERIALS AND METHODS: All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis and 14 were predominantly invasive ductal carcinomas (idc. RESULTS: EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%, HPV, 20% and MMTV (32% of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. CONCLUSIONS: We conclude that (i EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  18. 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.

  19. Magnetic Resonance Imaging after Completion of Neoadjuvant Chemotherapy Can Accurately Discriminate between No Residual Carcinoma and Residual Ductal Carcinoma In Situ in Patients with Triple-Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Seho Park

    Full Text Available The accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0 from residual ductal carcinoma in situ (ypTis in breast cancer patients who received NCT.Parameters of 117 patients attaining pathological complete response (CR in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI before and after NCT.There were 67 (57.3% patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR, 4.23; 95% confidence interval (CI, 1.11-16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53-17.85. Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5% were ypT0 after NCT.Among imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2-enriched tumors after NCT.

  20. 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.

  1. Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study

    Science.gov (United States)

    Solin, Lawrence J.; Gray, Robert; Hughes, Lorie L.; Wood, William C.; Lowen, Mary Ann; Badve, Sunil S.; Baehner, Frederick L.; Ingle, James N.; Perez, Edith A.; Recht, Abram; Sparano, Joseph A.; Davidson, Nancy E.

    2015-01-01

    Purpose To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. Patients and Methods A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. Results There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). Conclusion For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. PMID:26371148

  2. Subareolar Sclerosing Ductal Hyperplasia.

    Science.gov (United States)

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

    2017-02-01

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

  3. Differential expression of follistatin and FLRG in human breast proliferative disorders

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    Amaral Vania F

    2009-09-01

    Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

  4. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni;

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... determined and found to be indistinguishable. Comparison of the vitronectin and the hemoglobin concentrations of the extracts showed that their vitronectin content was not derived from blood contamination. Vitronectin mRNA was undetectable in both carcinomas and normal tissue. We conclude that vitronectin...

  5. Assessment of utility of ductal lavage and ductoscopy in breast cancer-a retrospective analysis of mastectomy specimens.

    Science.gov (United States)

    Badve, Sunil; Wiley, Elizabeth; Rodriguez, Norma

    2003-03-01

    Early detection of breast lesions continues to be an important goal in the management of breast cancer. At present, mammographic imaging in addition to physical examination is the main screening method for the detection of cancer. Fiberoptic ductoscopy and duct lavage are being recently used to evaluate patients at risk for breast cancer. Both techniques examine the nipple and central duct area to identify intraductal lesions. In this study, we examined the frequency of involvement of these structures in mastectomy specimens as a surrogate marker to estimate the utility of these methods in breast cancer patients. The presence and type of involvement of the nipple and central duct area was retrospectively evaluated in 801 mastectomy specimens from a 4-year period that had been performed for infiltrating or in situ carcinoma. Atypical proliferation or cells, when seen in the ducts of this region, was considered as evidence of nipple involvement, even if definite evidence of malignancy was lacking. The review of 801 mastectomies showed nipple and central duct involvement in 179 (22%) cases. Among the 665 cases of infiltrating carcinoma, 17% did not have an intraductal component. The relative rarity of nipple and central duct in mastectomy specimens and the lack of an in situ component in many cases raise questions about the utility of fiberoptic ductoscopy and duct lavage as methods for screening of breast cancer. Additionally, as these methods examine only 1-2 ducts of the 15-20 ducts that open at the nipple, they might fail to detect focal abnormalities.

  6. Storage of Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Gamze Can

    2007-10-01

    Full Text Available Storage of human breast milk by freezing or refrigeration of milk has been recommended especially at some social circumstances of most mothers who are regularly separated from their infants because of work. The greatest fear that has hindered the prospects of in - vitro storage of breast milk for any considerable period of time is the possibility of bacterial contamination and growth of infectious pathogens in the stored milk, there by rendering them unsafe for human consumption. The storage container can influence the cell content of milk, as the cells adhere to the walls of a glass container but not to polyethylene or polypropylene containers. Bacteriological examination of refrigerated milks has proven their safety for human consumption for even up to 72 h. For a storage over longer periods up to 1 month, freezing at - 20 0C could be recommended, but the most preferred method, especially for longer storage would be fresh freezing at - 70 0C, if affordable or available. The nutrient value of human milk is essentially unchanged, but the immunological properties are reduced by various storage techniques. Boiling and microwave radiation have not been recommended. [TAF Prev Med Bull 2007; 6(5.000: 375-379

  7. Recreational physical activity, anthropometric factors, and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Kim, Mimi; Wactawski-Wende, Jean; Lane, Dorothy; Adams-Campbell, Lucile L; Gaudet, Mia; Stefanick, Marcia L; Vitolins, Mara; Chlebowski, Rowan T; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2010-12-01

    To assess the association of recreational physical activity and anthropometric factors in relation to risk of ductal carcinoma in situ (DCIS) of the breast. The association was examined in a cohort of 58,055 postmenopausal women participating in the Women's Health Initiative (WHI) clinical trials, among whom 450 cases of DCIS were ascertained after a median follow-up of 8.0 years. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). After adjustment for covariates, the hazard ratio for DCIS among women with ≥ 20 metabolic equivalent task-hours per week (MET-h/week) of total recreational physical activity compared to women who did not engage in any recreational physical activity (0 MET-h/week) was 0.97 (95% CI 0.70-1.34). Neither body mass index nor waist circumference was associated with risk. In addition, physical activity and anthropometric factors were not associated with risk of either high-grade or low-/moderate-grade DCIS. Recreational physical activity and anthropometric factors showed no association with risk of DCIS in postmenopausal women in the WHI clinical trial.

  8. Impact of Nonosseous Findings on {sup 18}F-NaF PET/CT in a Patient with Ductal Breast Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kuyumcu, Serkan; Adalet, Isik; Isik, Emine Goknur; Unal, Seher Nilgun [Intanbul Univ., Istanbul (Turkmenistan)

    2014-03-15

    {sup 18}F-NaF was used as a bone-seeking PET tracer for skeletal imaging until the introduction of the widely available {sup 99m}Tc-labeled bone agents. However, there is renewed clinical interest in {sup 18}F-NaF since prior technical and logistic limitations to its routine use are no longer present, and, as a consequence, it is likely that uptake unrelated to bone and non-osseous findings will be encountered more frequently. As a result of tumoral necrosis, soft tissue metastases may demonstrate {sup 18}F-NaF avidity due to dystrophic calcification. On the other hand, all non-osseous findings, whether {sup 18}F-NaF avid or not, may provide important diagnostic information that may alter the course of the disease, including treatment options. Herein we present a patient with ductal carcinoma of the breast in whom findings unrelated to the skeletal system in {sup 18}F-NaF PET/CT altered the treatment strategy.

  9. Growth of human breast tissues from patient cells in 3D hydrogel scaffolds.

    Science.gov (United States)

    Sokol, Ethan S; Miller, Daniel H; Breggia, Anne; Spencer, Kevin C; Arendt, Lisa M; Gupta, Piyush B

    2016-03-01

    Three-dimensional (3D) cultures have proven invaluable for expanding human tissues for basic research and clinical applications. In both contexts, 3D cultures are most useful when they (1) support the outgrowth of tissues from primary human cells that have not been immortalized through extensive culture or viral infection and (2) include defined, physiologically relevant components. Here we describe a 3D culture system with both of these properties that stimulates the outgrowth of morphologically complex and hormone-responsive mammary tissues from primary human breast epithelial cells. Primary human breast epithelial cells isolated from patient reduction mammoplasty tissues were seeded into 3D hydrogels. The hydrogel scaffolds were composed of extracellular proteins and carbohydrates present in human breast tissue and were cultured in serum-free medium containing only defined components. The physical properties of these hydrogels were determined using atomic force microscopy. Tissue growth was monitored over time using bright-field and fluorescence microscopy, and maturation was assessed using morphological metrics and by immunostaining for markers of stem cells and differentiated cell types. The hydrogel tissues were also studied by fabricating physical models from confocal images using a 3D printer. When seeded into these 3D hydrogels, primary human breast epithelial cells rapidly self-organized in the absence of stromal cells and within 2 weeks expanded to form mature mammary tissues. The mature tissues contained luminal, basal, and stem cells in the correct topological orientation and also exhibited the complex ductal and lobular morphologies observed in the human breast. The expanded tissues became hollow when treated with estrogen and progesterone, and with the further addition of prolactin produced lipid droplets, indicating that they were responding to hormones. Ductal branching was initiated by clusters of cells expressing putative mammary stem cell

  10. Multicentric and contralateral invasive tumors identified with pre-op MRI in patients newly diagnosed with ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Hollingsworth, Alan B; Stough, Rebecca G

    2012-09-01

    Preoperative breast MRI in newly diagnosed cancer patients has several potential benefits. Improved survival for patients with invasive disease as the index lesion is unlikely to be one of these benefits, given what is known from variations in locoregional management in the historic conservation trials. However, this may not be the case for patients with ductal carcinoma in situ (DCIS), as the discovery of unsuspected invasive cancer located elsewhere from the biopsy-proven DCIS could result in decreased survival if left undetected and untreated. In support of this hypothesis, a previous observational study of a large cohort of DCIS patients revealed the development of invasive cancer to be the most common event after unilateral DCIS treatment, occurring in 3.9%, mostly in the opposite breast. These cancers appeared on mammography or clinical exam within a short time frame (median 2.9 years) and were associated with a diminution in survival. Given these second events occurring so soon after DCIS treatment, it must be considered that invasive cancers were present elsewhere, but mammographically occult, at the time of DCIS diagnosis. To examine this possibility, 288 consecutive patients with newly diagnosed DCIS underwent preoperative MRI, with the discovery of separate foci of invasive cancer, either multicentric or contralateral, occurring in 3.5% of patients, a similar incidence to the short-term observational study. These "elsewhere" invasive cancers are presented here with details of pathology such that both Stage I and Stage II disease can be seen as clinically significant, with the usual stage-based survival implications.

  11. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids

    Science.gov (United States)

    Huang, Ling; Holtzinger, Audrey; Jagan, Ishaan; BeGora, Michael; Lohse, Ines; Ngai, Nicholas; Nostro, Cristina; Wang, Rennian; Muthuswamy, Lakshmi B.; Crawford, Howard C.; Arrowsmith, Cheryl; Kalloger, Steve E.; Renouf, Daniel J.; Connor, Ashton A; Cleary, Sean; Schaeffer, David F.; Roehrl, Michael; Tsao, Ming-Sound; Gallinger, Steven; Keller, Gordon; Muthuswamy, Senthil K.

    2016-01-01

    There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation of human pluripotent stem cells (PSCs) into exocrine progenitor organoids that form ductal and acinar structures in culture and in vivo. Expression of mutant KRAS or TP53 in progenitor organoids induces mutation-specific phenotypes in culture and in vivo. Expression of TP53R175H induced cytosolic SOX9 localization. In patient tumors bearing TP53 mutations, SOX9 was cytoplasmic and associated with mortality. Culture conditions are also defined for clonal generation of tumor organoids from freshly resected PDAC. Tumor organoids maintain the differentiation status, histoarchitecture, phenotypic heterogeneity of the primary tumor, and retain patient-specific physiologic changes including hypoxia, oxygen consumption, epigenetic marks, and differential sensitivity to EZH2 inhibition. Thus, pancreatic progenitor organoids and tumor organoids can be used to model PDAC and for drug screening to identify precision therapy strategies. PMID:26501191

  12. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids.

    Science.gov (United States)

    Huang, Ling; Holtzinger, Audrey; Jagan, Ishaan; BeGora, Michael; Lohse, Ines; Ngai, Nicholas; Nostro, Cristina; Wang, Rennian; Muthuswamy, Lakshmi B; Crawford, Howard C; Arrowsmith, Cheryl; Kalloger, Steve E; Renouf, Daniel J; Connor, Ashton A; Cleary, Sean; Schaeffer, David F; Roehrl, Michael; Tsao, Ming-Sound; Gallinger, Steven; Keller, Gordon; Muthuswamy, Senthil K

    2015-11-01

    There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation of human pluripotent stem cells into exocrine progenitor organoids that form ductal and acinar structures in culture and in vivo. Expression of mutant KRAS or TP53 in progenitor organoids induces mutation-specific phenotypes in culture and in vivo. Expression of TP53(R175H) induces cytosolic SOX9 localization. In patient tumors bearing TP53 mutations, SOX9 was cytoplasmic and associated with mortality. We also define culture conditions for clonal generation of tumor organoids from freshly resected PDAC. Tumor organoids maintain the differentiation status, histoarchitecture and phenotypic heterogeneity of the primary tumor and retain patient-specific physiological changes, including hypoxia, oxygen consumption, epigenetic marks and differences in sensitivity to inhibition of the histone methyltransferase EZH2. Thus, pancreatic progenitor organoids and tumor organoids can be used to model PDAC and for drug screening to identify precision therapy strategies.

  13. 不同雌激素受体亚型在乳腺浸润性导管癌中的分布及意义%Distribution and significance of three subtypes of ER in breast invasive ductal cancers

    Institute of Scientific and Technical Information of China (English)

    周春; 罗浩军; 李维东; 涂刚

    2013-01-01

    Objective: To evaluate the distribution and significance of the three subtypes of estrogen receptor (ER) in mammary invasive ductal cancer. Methods: Immunohistochemistry was used to detect Era, Erβf! And estrogen (G protein coupled) receptor (GPER) in paraffin - embedded tissues of invasive ductal cancers from 135 patients. The expression of Ers was correlated to clinicopathological variables via Chi - square and t - test. Association analysis was preformed among these three subtypes of ER as well, In addition, mean Nottingham prognostic index was compared by one - way analysis of variance among subgroups of tumor with variable ER phenotype. Results:Era,ER and GPER were detected in 53.3%, 64.7% and 74.8% of these 135 samples respectively. However, there was no significant association among them. Era expression was correlated to progesterone receptor and human epidermal growth factor receptor - 2 significantly. While, no statistical association was found between ER, as well as GPER, and anyone of clinicopathological variables detected. Interestingly, the mean Nottingham prognostic index was larger in Era - Erβ - GPER - tumors comparing to Era + ER|3 + GPER - (P = 0.046) and Era + ER + GPER + (P = 0.022) ones in the analysis among subgroups of tumor with different ER phenotype. Conclusions: Any of Era,ERP and GPER was widely distributed in invasive ductal cancers. Thus, all of them could be involved in the estrogenic response in breast cancer. Furthermore, Era.ER and GPER are three independent subtypes of ER and analysis of their phenotype would be essential for the study of estrogenic effects in breast cancers.%目的:探讨三种雌激素受体(estrogen receptor,ER)亚型(ERα、ERβ及雌激素G蛋白偶联受体estrogen [G protein coupled) receptor,GPER)在乳腺浸润性导管癌中的分布与意义.方法:应用免疫组织化学法检测135例石蜡包埋浸润性导管癌组织中ERα、ERβ及GPER蛋白的表达,用x2检验等方法分析其与临床病

  14. Associação entre a presença da proteína p53 e o grau de diferenciação em carcinomas ductais invasivos de mama Association of p53 protein expression and degree of differentiation in infiltrating ductal breast carcinomas

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    Márcia Sanae Siroma

    2006-05-01

    Full Text Available OBJETIVO: avaliar a expressão da proteína p53 no carcinoma de mama ductal invasivo e avaliar a sua associação com o grau histológico e o grau nuclear. MÉTODOS: foram incluídas sessenta e cinco mulheres atendidas consecutivamente, entre julho de 1999 e julho de 2001. Todas tiveram diagnóstico de carcinoma primário de mama ductal invasivo. As pacientes foram primeiramente tratadas por terapia cirúrgica conservadora ou mastectomia. Nenhuma paciente recebeu terapia neoadjuvante. Os espécimes cirúrgicos dos tumores foram fixados em formalina a 10%, posteriormente incluídos em parafina e conservados para análise imuno-histoquimica. A expressão da proteína p53 foi avaliada. Foi utilizado o anticorpo primário monoclonal anti-humano p53 DO - 7 (DAKO. As distribuições das freqüências foram avaliadas pelo teste do chi2. O valor pPURPOSE: to assess p53 protein expression in infiltrating ductal breast carcinoma and to analyze its association with histological and nuclear grade. METHODS: sixty-five consecutive females who were diagnosed with primary infiltrating ductal breast tumor from July 1999 to July 2001 were included in the present study. Mean patient age at diagnosis was 69.2 years (range 41 - 90. All patients were first treated with surgical therapy, conservative surgery or mastectomy. None of the patients received any preoperative adjuvant therapy. Resected breast tumor specimens were fixed in 10% formalin, paraffin embedded, and conserved for immunohistochemical analysis. p53 protein expression was evaluated. Primary monoclonal anti-human p53 antibody DO-7 (DAKO was used. Frequency distributions were tested by the chi2 test. A level of p<0,05 was considered significant. RESULTS: p53 expression was detected in 24 (36,9% of 65 carcinomas. Of the cases with protein expression, 13 (54,2% were high or histological grade III, 8 (33,3%, were grade II, 3 (12,5% were grade I. On nuclear grade analysis, of the cases with protein

  15. CYTOKINE-PRODUCING RESERVE OF IMMUNOCOMPETENT CELLS FROM BLOOD AND INVASIVE DUCTAL BREAST CANCER TISSUES: ITS CORRELATION WITH HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL PARAMETERS OF MALIGNANT NEOPLASIA

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    S. A. Arkhipov

    2016-01-01

    Full Text Available The aim of the study was to investigate a relationship between cytokine-producing reserve of invasive ductal cancer cells and its microenvironment, and cytokine-producing reserve of immunocompetent blood cells (IBC, as well as with histopathological and immunohistochemical characteristics of breast cancer. Using ELISA method we investigated the spontaneous and stimulated with polyclonal activators (PA cytokine-producing reserve of IBC and biopsy specimens from invasive ductal cancer (adenocarcinoma in 34 women. Appropriate values were expressed by the Influence Index of polyclonal activators (IIPA upon cytokine production (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF-A, MCP-1. In tumor biopsies, we studied expression of VEGF-A, estrogen receptor, progesteron receptor and pro-proliferation marker Ki-67 by means of immunohistochemical method. Activation values of blood IBC in most cases, except of IL-18, IL-1β and MCP-1, were higher than appropriate effects upon cytokine production by tumor tisuues. Meanwhile, the IIPA activation index upon IL-18 (a proinflammatory and prooncogene cytokine production by tumor cells and its microenvironment proved to be elevated, as compared to appropriate IIPA by the blood IBC. Statistical studies showed a direct correlation between IIPA and cytokine production in tumor supernates, IIPA of VEGF-A expression in tumor tissue, with pathohistological parameters and expression of estrogen and progesterone receptors and Ki-67 proliferation marker. A high positive correlation was obtained between IIPA TNFα production by the tumor tissue, and degree of tumor vascularization.We have revealed a negative correlation between IIPA for IL-6, MCP-1 and Ki-67 marker of cell proliferation. A direct correlation was found between IIPA values for IL-1ra/IL-1β production ratios in blood cells, and IIPA for VEGF-A expression in adenocarcinoma tissues, thus indicating to probable

  16. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

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    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  17. High fibroblast growth factor 19 (FGF19) expression predicts worse prognosis in invasive ductal carcinoma of breast.

    Science.gov (United States)

    Buhmeida, Abdelbaset; Dallol, Ashraf; Merdad, Adnan; Al-Maghrabi, Jaudah; Gari, Mamdooh A; Abu-Elmagd, Muhammad M; Chaudhary, Adeel G; Abuzenadah, Adel M; Nedjadi, Taoufik; Ermiah, Eramah; Al-Thubaity, Fatima; Al-Qahtani, Mohammed H

    2014-03-01

    Metabolic diseases like diabetes and obesity are major risk factors for breast cancer. Aberrant expression of metabolic effectors such as fibroblast growth factor 19 (FGF19) could be therefore associated with the disease. The expression of FGF19 was examined in 193 archival breast tumor samples by immunohistochemistry and evaluated semi-quantitatively by determining the staining index and correlating it with clinicopathological parameters using Fisher's exact test. The correlation between FGF19 expression and 5-year disease-specific survival rate was determined using the univariate Kaplan-Meier analysis. The prognostic value of FGF19 expression was evaluated using the multivariate Cox regression analysis. Of the 193 tumors analyzed, 40% were classified with low FGF19 expression, whereas 60% were categorized as tumors with high FGF19 expression. There was a highly significant correlation between high FGF19 expression and patients' age (p = 0.008) as well as 5-year disease-specific survival (p = 0.001). However, FGF19 expression did not show any significant correlations with other clinicopathological parameters, including hormonal status, tumor grade, tumor size, or lymph node status. Univariate Kaplan-Meier log rank analysis showed that patients with high FGF19 expression exhibited a significantly shorter disease-specific 5-year survival (p = 0.007). This effect was exacerbated by lymph node metastasis (p = 0.001), negative estrogen receptor (ER) status (p = 0.002), or old age (p = 0.013). Multivariate analysis showed that high FGF19 expression could be an independent prognostic marker of disease-specific survival in breast cancer patients (p = 0.030). Quantification of FGF19 expression appears to provide valuable prognostic information in breast cancer, particularly in older patients with lymph node metastasis and negative ER status.

  18. Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study

    Science.gov (United States)

    Duffy, Stephen W; Dibden, Amanda; Michalopoulos, Dimitrios; Offman, Judith; Parmar, Dharmishta; Jenkins, Jacquie; Collins, Beverley; Robson, Tony; Scorfield, Suzanne; Green, Kathryn; Hall, Clare; Liao, Xiao-Hui; Ryan, Michael; Johnson, Fiona; Stevens, Guy; Kearins, Olive; Sellars, Sarah; Patnick, Julietta

    2016-01-01

    Summary Background The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. Methods We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50–64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers. Findings We analysed data for 5 243 658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 1·54–3·56] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient −0·084 [95% CI −0·13 to −0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after

  19. An Improved Breast Epithelial Sampling Method for Molecular Profiling and Biomarker Analysis in Women at Risk for Breast Cancer.

    Science.gov (United States)

    Danforth, David N; Warner, Andrew C; Wangsa, Darawalee; Ried, Thomas; Duelli, Dominik; Filie, Armando C; Prindiville, Sheila A

    2015-01-01

    There is a strong need to define the molecular changes in normal at-risk breast epithelium to identify biomarkers and new targets for breast cancer prevention and to develop a molecular signature for risk assessment. Improved methods of breast epithelial sampling are needed to promote whole-genome molecular profiling, increase ductal epithelial cell yield, and reduce sample cell heterogeneity. We developed an improved method of breast ductal sampling with ductal lavage through a 22-gauge catheter and collection of ductal samples with a microaspirator. Women at normal risk or increased risk for breast cancer were studied. Ductal epithelial samples were analyzed for cytopathologic changes, cellular yield, epithelial cell purity, quality and quantity of DNA and RNA, and use in multiple downstream molecular applications. We studied 50 subjects, including 40 subjects at normal risk for breast cancer and 37 subjects with non-nipple aspirate fluid-yielding ducts. This method provided multiple 1.0 mL samples of high ductal epithelial cell content (median ≥8 samples per subject of ≥5,000 cells per sample) with 80%-100% epithelial cell purity. Extraction of a single intact ductal sample (fluid and cells) or the separate frozen cellular component provided DNA and RNA for multiple downstream studies, including quantitative reverse transcription- polymerase chain reaction (PCR) for microRNA, quantitative PCR for the human telomerase reverse transcriptase gene, whole-genome DNA amplification, and array comparative genomic hybridization analysis. An improved breast epithelial sampling method has been developed, which should significantly expand the acquisition and biomarker analysis of breast ductal epithelium in women at risk for breast cancer.

  20. Effect of Quantitative Nuclear Image Features on Recurrence of Ductal Carcinoma In Situ (DCIS of the Breast

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    Judith-Anne W. Chapman

    2008-01-01

    Full Text Available Background: Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence.Methods: Hematoxylin and eosin stained slides for a cohort of 80 patients with primary breast DCIS were reviewed and two fields with representative grade (or grades were identified by a Pathologist and simultaneously used for acquisition of digital images for each field. Van Nuys worst nuclear grade was assigned, as was predominant grade, and heterogeneous grading when present. Patients were grouped by heterogeneity of their nuclear grade: Group A: nuclear grade 1 only, nuclear grades 1 and 2, or nuclear grade 2 only (32 patients, Group B: nuclear grades 1, 2 and 3, or nuclear grades 2 and 3 (31 patients, Group 3: nuclear grade 3 only (17 patients. Nuclear fi ne structure was assessed by software which captured thirty-nine nuclear feature values describing nuclear morphometry, densitometry, and texture. Step-wise forward Cox regressions were performed with previous clinical and pathologic factors, and the new image analysis features.Results: Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. The rate of correct classification of nuclear grading with digital image analysis features was similar in the two fields, and pooled assessment across both fields. In the pooled assessment, a discriminant function with one nuclear morphometric and one texture feature was significantly (p = 0.001 associated with nuclear grading, and provided correct jackknifed classification of a patient’s nuclear grade for Group A (78.1%, Group B (48.4%, and Group C (70.6%. The

  1. Aluminium in human breast tissue.

    Science.gov (United States)

    Exley, Christopher; Charles, Lisa M; Barr, Lester; Martin, Claire; Polwart, Anthony; Darbre, Philippa D

    2007-09-01

    Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.

  2. Retrospective analysis of 108 ductal carcinomas in situ of the breast treated by radiosurgery association; Analyse retrospective de 108 carcinomes canalaires in situ mammaires traites par association radiochirurgicale

    Energy Technology Data Exchange (ETDEWEB)

    Fourneret, P.; Artignan, X.; Cornulier, J. de; Kolodie, H.; Vincent, F.; Colona, M.; Bolla, M. [CHU de Grenoble, Service de cancerologie-radiotherapie, 38 - Grenoble (France); Pasquier, D. [CHU de Grenoble, Service d' anatomopathologie, 38 - Grenoble (France); Bernard, P. [CHU de Grenoble, Service de gynecologie, 38 - Grenoble (France); Payan, R. [Clinique Belledone, 38 - Saint-Martin-D' Heres (France); Frice, D. [Clinique du Mail, 38 - Grenoble (France); Colona, M.; Bolla, M. [Office Dept. de lutte contre le cancer, 38 - Meylan (France); Panh, M.H. [Registre du cancer de l' Isere, 38 - Meylan (France)

    2006-12-15

    Purpose. - To evaluate survival and prognostic factors of 108 patients with clinically or mammo-graphically detected ductal carcinoma in situ (DCIS), treated from 1980 to 1996 by complete local excision followed by external irradiation. Patients and methods. - The median age was 51 (range 37-80). All the patients underwent surgery consisting of a wide resection of the mammary gland harboring the tumour. The surgical specimens were sent to the pathologists to get information on histology and margin clearance; all the slides were reviewed by one of us to assess the tumoral diameter. External beam therapy was delivered within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25 fractions to be given in 5 weeks. The median duration of follow-up was 93 months (range 40-173). Results. - There were nine patients with local recurrence (8.3%); three patients had local recurrence of DCIS and six patients developed invasive breast cancer. The treatment of local recurrence consisted of mastectomy with or without axillary dissection (eight cases) and quadrant-ectomy (one case). The 5-year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%. The 10-year cause specific survival was 100%. In univariate analysis, size {>=} 10 mm, age < 45 years old and margin status were significant P = 0,02. P 0,03, P = 0,005; margin status was significant in multivariate analysis (P < 0,02). Conclusion. - These results are in keeping with those of the literature. They could be improved by the mass screening campaign, which is going on since January 1990 among women aged 50 - 74 years. (authors)

  3. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  4. 乳腺导管扩张积乳合并感染的超声图像特征分析%Sonogram in Ductal Ectasia of Breast Concurrent Infection

    Institute of Scientific and Technical Information of China (English)

    韩伟; 王颖鑫; 高军喜; 姚兰辉

    2012-01-01

    Objective To investigate the characteristics of sonogram in the ductal ectasia of breast concurrent infection. Methods A retrospective analysis was performed on 20 cases of ductal ectasia of breast concurrent infection, 30 cases fibroadenoma and 30 cases focal Hyperplastic nodule diagnosed by ultrasound and pathological. Results The higher internal wall echoes,internal echo uniformity, bloodstream and distance from the nipples among ductal ectasia of the breast concurrent infection,fibroadenoma and the focal Hyperplastic nodule had statistical significance (P0. 05). Conclusions 2-Dimensional and color doppler ultrasound can elevate the accurate of diagnosis in the ductal ectasia of breast concurrent infection and distinguish from fibroadenoma and focal Hyperplastic nodule.%目的 探讨乳腺导管扩张积乳合并感染的超声图像特征.方法 对超声诊断并经手术病理证实的乳腺导管扩张积乳合并感染的20例患者与同时期经超声诊断并经手术病理证实的30例乳腺纤维腺瘤及30例乳腺局灶性增生结节的患者进行对照分析.结果 三者两两比较,在高回声边壁、内部回声,内部血流及距乳头距离方面差异具有统计学意义(P<0.05),导管扩张积乳合并感染往往以乳头下更为常见,多数无血流信号分布.而三者在象限分布、纵横比、边界、形态,内部钙化等方面比较差异均无统计学意义(P>0.05).结论 结合二维及彩色多普勒超声能够提高对乳腺导管扩张积乳合并感染诊断的准确性,并可与纤维腺瘤及局灶性增生等良性病变进行鉴别.

  5. Hyperplasia (Ductal or Lobular)

    Science.gov (United States)

    ... Adenosis of the Breast Fibroadenomas of the Breast Phyllodes Tumors of the Breast Intraductal Papillomas Granular Cell Tumors ... Adenosis of the Breast Fibroadenomas of the Breast Phyllodes Tumors of the Breast Intraductal Papillomas Granular Cell Tumors ...

  6. Myoepithelial cell differentiation markers in ductal carcinoma in situ progression.

    Science.gov (United States)

    Russell, Tanya D; Jindal, Sonali; Agunbiade, Samiat; Gao, Dexiang; Troxell, Megan; Borges, Virginia F; Schedin, Pepper

    2015-11-01

    We describe a preclinical model that investigates progression of early-stage ductal carcinoma in situ (DCIS) and report that compromised myoepithelial cell differentiation occurs before transition to invasive disease. Human breast cancer MCF10DCIS.com cells were delivered into the mouse mammary teat by intraductal injection in the absence of surgical manipulations and accompanying wound-healing confounders. DCIS-like lesions developed throughout the mammary ducts with full representation of human DCIS histologic patterns. Tumor cells were incorporated into the normal mammary epithelium, developed ductal intraepithelial neoplasia and DCIS, and progressed to invasive carcinoma, suggesting the model provides a rigorous approach to study early stages of breast cancer progression. Mammary glands were evaluated for myoepithelium integrity with immunohistochemical assays. Progressive loss of the myoepithelial cell differentiation markers p63, calponin, and α-smooth muscle actin was observed in the mouse myoepithelium surrounding DCIS-involved ducts. p63 loss was an early indicator, calponin loss intermediate, and α-smooth muscle actin a later indicator of compromised myoepithelium. Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. In single time point biopsies obtained from 16 women diagnosed with pure DCIS, a similar loss in myoepithelial cell markers was observed. These results suggest that further research is warranted into the role of myoepithelial cell p63 and calponin expression on DCIS progression to invasive disease.

  7. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Becerra, Rocio [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Diaz, Lorenza, E-mail: lorenzadiaz@gmail.com [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Camacho, Javier [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico); Barrera, David; Ordaz-Rosado, David; Morales, Angelica [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Ortiz, Cindy Sharon [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Avila, Euclides [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Bargallo, Enrique [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Arrecillas, Myrna [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Halhali, Ali; Larrea, Fernando [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)

    2010-02-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  8. Ductal carcinoma in situ: a challenging disease

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    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

  9. Epidermal growth factor (EGF and interleukin (IL-1β synergistically promote ERK1/2-mediated invasive breast ductal cancer cell migration and invasion

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    Ma Liqiang

    2012-10-01

    Full Text Available Abstract Background Patients with invasive breast ductal carcinoma (IBDC with metastasis have a very poor prognosis. Little is known about the synergistic action of growth and inflammatory factors in IBDC metastases. Methods The expression of activated extracellular signal-regulated kinase1/2 (phosphorylated or p-ERK1/2 was analyzed by immunohistochemistry in IBDC tissue samples from 80 cases. BT474 IBDC cell migration and invasion were quantified using the Transwell assay. Matrix metalloproteinase (MMP-9 expression and activity were analyzed by RT-PCR, Western blotting and zymography. Activator protein (AP-1 activity was measured with a luciferase reporter gene assay. The Wilcoxon signed-rank test, Chi-square test, the partition of Chi-square test, independent t-test, and Spearman’s method were used for the statistical analysis. Results Phosphorylated ERK1/2 was detected in 58/80 (72.5% IBDC tissues, and was associated with higher TNM stage and lymph node metastasis, but not patient age or tumor size. Individually, epidermal growth factor (EGF, and interleukin (IL-1β activated ERK1/2, increased cell migration and invasion, MMP-9 expression and activity, AP-1 activation in vitro and the expression of p-ERK1/2 was positively correlated with EGF expression levels, as well as IL-1β, MMP-9 and c-fos in IBDC tissue samples. Co-stimulation with EGF and IL-1β synergistically increased ERK1/2 and AP-1 activation, cell migration and invasion, and MMP-9 expression and activity. Inhibition of ERK1/2 using U0126 or siRNA abolished EGF and/or IL-1β-induced cell migration and invasion in a dose-dependent manner. Conclusion Activated ERK1/2 was associated with higher TNM stage and lymph node metastasis in IBDC. Both in vitro and in vivo studies indicated that ERK-1/2 activation may increase the metastatic ability of IBDC cells. Growth and inflammatory factors synergistically induced IBDC cell migration and invasion via ERK1/2 signaling, AP-1 activation

  10. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  11. MRI Diagnosis of Breast Ductal Carcinoma in Situ%乳腺MRI对导管原位癌及其微浸润的诊断

    Institute of Scientific and Technical Information of China (English)

    梅昂; 华佳

    2011-01-01

    Objective To assess diagnostic value of MRI for breast ductal carcinoma in situ( DCIS). Methods MRI and mammography data in 13 women with breast DCIS and DCIS with microinvasion (DCIS-Mi) confirmed by pathology were retrospectively and comparativcly analyzed with pathologic examination. Results In 13 cases underwent contrast-enhanced dynamic MR imaging,11 lesions showed non-mass-like enhancement. In 10 patients underwent mammography, one case showed negative result. Regarding the BI-RADS Ⅳ or Ⅴ as the positive standard , there was not significant difference in accurate diagnostic rate between MRI and mammography(P=O. 353). Regarding the extent of the lesions measured on pathologic examination as gold standard, 10 cases in MRI and 6 cases in mammography were corresponded,2 lesions overestimated extent by MRI and mammography , respectively, and one lesion underestimated by mammography. The difference was not significant ( P = 0. 277). Conclusion MR imaging features of DCIS and DCIS-Mi were characteristic certainly. MR imaging combined with mammography can improve the detecting rate and diagnostic accuracy of DCIS.%目的 探讨乳腺MRI对导管原位癌及其微浸润的诊断价值.方法 回顾性分析经手术病理证实的乳腺导管原位癌及导管原位癌伴微浸润病例 13例,所有病例均于术前行动态增强MRI检查,其中 10例同时行钼靶X线检查.结果 MR检查13例病灶中11例表现为非肿块样强化,10例行钼靶X线检查,1例阴性,以BIRADS分级中的4、5级为MR和X线检查的阳性指标,其正确诊断率差异无统计学意义(P=0.353).以病理结果为金标准,MRI界定病灶范围符合10例,高估2例,钼靶X线符合6例,高估2例,低估1例,差异无统计学意义(P=0.277).结论 乳腺MRI对导管原位癌及导管原位癌伴微浸润有其特征性表现,钼靶X线和MR检查相结合能提高早期导管原位癌的检出率及正确诊断率.

  12. 乳腺浸润性导管癌25例的临床及MRI表现分析%Analysis of clinical and MRI manifestation of 25 cases of infiltrating ductal carcinoma of the breast

    Institute of Scientific and Technical Information of China (English)

    李智晞

    2014-01-01

    目的:讨论乳腺浸润性导管癌的临床及MRI表现。方法:回顾性分析25例乳腺浸润性导管癌的临床及MRI表现。结果:乳腺浸润性导管癌好发于右乳外上象限,病理分级为Ⅱ级最多,MRI 上病灶多呈形态不规则的团块状,部分也可呈结节状及分叶状,T1WI呈等信号,T2WI呈稍高信号,DWI多呈高信号影,ADC值降低,20例可见病灶周围多发增生的肿瘤血管影。动态增强扫描,按TIC分型,Ⅰ型(渐增型)5例,Ⅱ型(平台型)11例,Ⅲ型(流出型)9例。结论:乳腺浸润性导管癌在临床及MRI表现上具有较明显的特征。%Objective:To explore the clinical and MRI manifestation.Methods:We retrospectively analyzed the clinical and MRI manifestation in 25 cases of invasive ductal carcinoma of the breast.Results:The primary site of infiltrating ductal carcinoma of the breast was right breast upper outer quadrant.The Ⅱ grade of pathologic grade was most.In MRI,lesion morphology most were irregular.Part were nodular or lobulated.T1WI was equisignal.T2WI was slightly high signal.The DWI was high signal.ADC values were reduced.There were multiple hyperplasia tumor vessels shadow in 20 cases around the focus.On dynamic enhanced scan, according to TIC classification,5 cases were type Ⅰ type(incremental type),11 cases were Ⅱ type(platform type),and 9 cases wereⅢ type(outflow type).Conclusion:There are obvious character of infiltrating ductal carcinoma of the breast in clinical and MRI manifestation.

  13. Epigenetic Effects of Human Breast Milk

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    Elvira Verduci

    2014-04-01

    Full Text Available A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

  14. Timing of critical genetic changes in human breast disease.

    Science.gov (United States)

    Ellsworth, Rachel E; Ellsworth, Darrell L; Deyarmin, Brenda; Hoffman, Laurel R; Love, Brad; Hooke, Jeffrey A; Shriver, Craig D

    2005-12-01

    Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of genomic instability. Laser-microdissected DNA samples were collected from histologically normal breast specimens (n = 25), atypical ductal hyperplasia (ADH, n = 16), ductal carcinoma-in-situ (DCIS, n = 37), and stage I to III invasive carcinomas (n = 72). Fifty-two microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer were used to assess patterns of AI. AI frequencies were .0001). DCIS lesions contain levels of genomic instability that are characteristic of advanced invasive tumors, and this suggests that the biology of a developing carcinoma may already be predetermined by the in situ stage. Observations that levels of AI in ADH lesions are similar to those in disease-free tissues provide a genomic rationale for why prevention strategies at the ADH level are successful and why cases with ADH involving surgical margins do not require further resection.

  15. STUDY ON NUCLEAR MATRIX PROTEINS FROM HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    HE Qian; ZHANG Shu-qun; CHU Yong-lie; JIA Xiao-li; JIANG Jian-tao

    2009-01-01

    Objective To investigate the marker protein of human breast carcinoma from nuclear matrix proteins (NMPs).Methods NMPs were injected subcutaneously into rabbit to get antiserum, which was used to detect the NMPs specificity for breast carcinoma.Results There was an apparent positive band (100kD) in the NMPs of breast carcinoma, which did not exist in normal breast and other tumors that were detected.Conclusion One or one group of 100kD NMPs were found to be related to human breast carcinoma, which may be involved in the carcinogenesis and development of human breast carcinoma and valuable for breast carcinoma diagnosis.

  16. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  17. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  18. Squamoid eccrine ductal carcinoma.

    Science.gov (United States)

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence.

  19. Squamoid eccrine ductal carcinoma*

    Science.gov (United States)

    Saraiva, Maria Isabel Ramos; Vieira, Marcella Amaral Horta Barbosa; Portocarrero, Larissa Karine Leite; Fraga, Rafael Cavanellas; Kakizaki, Priscila; Valente, Neusa Yuriko Sakai

    2016-01-01

    Squamoid eccrine ductal carcinoma is an eccrine carcinoma subtype, and only twelve cases have been reported until now. It is a rare tumor and its histopathological diagnosis is difficult. Almost half of patients are misdiagnosed as squamous cell carcinoma by the incisional biopsy. We report the thirteenth case of squamoid eccrine ductal carcinoma. Female patient, 72 years old, in the last 6 months presenting erythematous, keratotic and ulcerated papules on the nose. The incisional biopsy diagnosed squamoid eccrine ductal carcinoma. After excision, histopathology revealed positive margins. A wideningmargins surgery and grafting were performed, which again resulted in positive margins. The patient was then referred for radiotherapy. After 25 sessions, the injury reappeared. After another surgery, although the intraoperative biopsy showed free surgical margins, the product of resection revealed persistent lesion. Distinction between squamoid eccrine ductal carcinoma and squamous cell carcinoma is important because of the more aggressive nature of the first, which requires wider margins surgery to avoid recurrence. PMID:28099603

  20. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    Science.gov (United States)

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth.

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

    Science.gov (United States)

    Bezić, Joško; Karaman, Ivana; Kunac, Nenad

    2016-01-01

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

  2. Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype

    Science.gov (United States)

    Johanning, Gary L.; Malouf, Gabriel G.; Zheng, Xiaofeng; Esteva, Francisco J.; Weinstein, John N.; Wang-Johanning, Feng; Su, Xiaoping

    2017-01-01

    Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer. PMID:28165048

  3. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    Science.gov (United States)

    2016-07-12

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  4. Stem cells in the human breast

    DEFF Research Database (Denmark)

    Petersen, Ole William; Polyak, Kornelia

    2010-01-01

    The origins of the epithelial cells participating in the development, tissue homeostasis, and cancer of the human breast are poorly understood. However, emerging evidence suggests a role for adult tissue-specific stem cells in these processes. In a hierarchical manner, these generate the two main...

  5. Human milk oligosaccharides: only the breast.

    Science.gov (United States)

    McVeagh, P; Miller, J B

    1997-08-01

    Over 100 years ago it was first deduced that a major component of human milk must be an unidentified carbohydrate that was not found in cows milk. At first this was thought to be a form of lactose and was called gynolactose. We now know that this was not a single carbohydrate but a complex mixture of approximately 130 different oligosaccharides. Although small amounts of a few oligosaccharides have been found in the milk of other mammals, this rich diversity of sugars is unique to human milk. The oligosaccharide content of human milk varies with the infant's gestation, the duration of lactation, diurnally and with the genetic makeup of the mother. Milk oligosaccharides have a number of functions that may protect the health of the breast fed infant. As they are not digested in the small intestine, they form the 'soluble' fibre of breast milk and their intact structure is available to act as competitive ligands protecting the breast-fed infant from pathogens. There is a growing list of pathogens for which a specific oligosaccharide ligand has been described in human milk. They are likely to form the model for future therapeutic and prophylactic anti-microbials. They provide substrates for bacteria in the infant colon and thereby contribute to the difference in faecal pH and faecal flora between breast and formula-fed infants. They may also be important as a source of sialic acid, essential for brain development.

  6. Freqüência de mutação no códon 12 do gene K-ras no carcinoma ductal invasivo de mama Frequency of mutations at codon 12 of the K--ras gene in invasive ductal breast cancer

    Directory of Open Access Journals (Sweden)

    Sônia Maria Rolim Rosa Lima

    1999-04-01

    Full Text Available Objetivo: pesquisar a freqüência de mutação pontual no códon 12 do gene K-ras, em espécimes cirúrgicos de pacientes portadoras de carcinoma ductal invasivo de mama. Material e Métodos: foram utilizados cortes de 50 espécimes cirúrgicos incluídos em blocos de parafina, de pacientes portadoras de carcinoma ductal invasivo de mama, com graus histológicos II e III. Os cortes destinados ao estudo foram desparafinizados e submetidos a extração do DNA, por meio do emprego da proteinase K. Para a amplificação do fragmento a ser analisado, utilizou-se a reação em cadeia da polimerase, seguida por clivagem com o emprego de enzima de restrição de comprimento variável (RFLP. A verificação da presença de mutação nas amostras foi feita com o emprego de eletroforese em gel de agarose, com marcador de peso molecular "Ladder 123" (GIBCO-BRL, e a documentação dos resultados, mediante fotografia, utilizando-se luz ultravioleta transmitida. Resultados: em cinco dos 50 carcinomas ductais invasivos de mama estudados (10% constatou-se a presença de mutação no códon 12 do gene K-ras, sendo todas elas polimórficas para esse caráter. As afetadas pelos tumores, que apresentavam a referida mutação, encontravam-se na pós-menopausa. Em quatro dos cinco casos em que se constatou a mutação, o grau histológico dos tumores era II e no caso restante III.Purpose: the frequency of point mutation at codon 12 of the K¾ras gene was determined in paraffin blocks of surgical specimens from patients who had ductal invasive breast cancer. Material and Methods: Fifty surgical specimens blocked in paraffin from patients with ductal invasive breast cancer, with histological degree II and III, were used. The polymerase chain reaction (PCR was used for amplification of DNA fragments studied. The material cleavage was obtained with restriction fragment length polymorphisms (RFLP. The electrophoresis in agarose gel, with Ladder 123 (GIBCO-BRL marker, was

  7. Lactation in the Human Breast From a Fluid Dynamics Point of View.

    Science.gov (United States)

    Negin Mortazavi, S; Geddes, Donna; Hassanipour, Fatemeh

    2017-01-01

    This study is a collaborative effort among lactation specialists and fluid dynamic engineers. The paper presents clinical results for suckling pressure pattern in lactating human breast as well as a 3D computational fluid dynamics (CFD) modeling of milk flow using these clinical inputs. The investigation starts with a careful, statistically representative measurement of suckling vacuum pressure, milk flow rate, and milk intake in a group of infants. The results from clinical data show that suckling action does not occur with constant suckling rate but changes in a rhythmic manner for infants. These pressure profiles are then used as the boundary condition for the CFD study using commercial ansys fluent software. For the geometric model of the ductal system of the human breast, this work takes advantage of a recent advance in the development of a validated phantom that has been produced as a ground truth for the imaging applications for the breast. The geometric model is introduced into CFD simulations with the aforementioned boundary conditions. The results for milk intake from the CFD simulation and clinical data were compared and cross validated. Also, the variation of milk intake versus suckling pressure are presented and analyzed. Both the clinical and CFD simulation show that the maximum milk flow rate is not related to the largest vacuum pressure or longest feeding duration indicating other factors influence the milk intake by infants.

  8. An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development.

    Science.gov (United States)

    Teoh, Kean-Hooi; Looi, Lai-Meng; Sabaratnam, Subathra; Cheah, Phaik-Leng; Nazarina, Abdul Rahman; Mun, Kein-Seong

    2011-06-01

    Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.

  9. 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.

  10. A complex 3D human tissue culture system based on mammary stromal cells and silk scaffolds for modeling breast morphogenesis and function.

    Science.gov (United States)

    Wang, Xiuli; Sun, Lin; Maffini, Maricel V; Soto, Ana; Sonnenschein, Carlos; Kaplan, David L

    2010-05-01

    Epithelial-stromal interactions play a crucial role in normal embryonic development and carcinogenesis of the human breast while the underlying mechanisms of these events remain poorly understood. To address this issue, we constructed a physiologically relevant, three-dimensional (3D) culture surrogate of complex human breast tissue that included a tri-culture system made up of human mammary epithelial cells (MCF10A), human fibroblasts and adipocytes, i.e., the two dominant breast stromal cell types, in a Matrigel/collagen mixture on porous silk protein scaffolds. The presence of stromal cells inhibited MCF10A cell proliferation and induced both alveolar and ductal morphogenesis and enhanced casein expression. In contrast to the immature polarity exhibited by co-cultures with either fibroblasts or adipocytes, the alveolar structures formed by the tri-cultures exhibited proper polarity similar to that observed in breast tissue in vivo. Only alveolar structures with reverted polarity were observed in MCF10A monocultures. Consistent with their phenotypic appearance, more functional differentiation of epithelial cells was also observed in the tri-cultures, where casein alpha- and -beta mRNA expression was significantly increased. This in vitro tri-culture breast tissue system sustained on silk scaffold effectively represents a more physiologically relevant 3D microenvironment for mammary epithelial cells and stromal cells than either co-cultures or monocultures. This experimental model provides an important first step for bioengineering an informative human breast tissue system, with which to study normal breast morphogenesis and neoplastic transformation.

  11. Human breast biomonitoring and environmental chemicals: use of breast tissues and fluids in breast cancer etiologic research.

    Science.gov (United States)

    LaKind, Judy S; Wilkins, Amy A; Bates, Michael N

    2007-09-01

    Extensive research indicates that the etiology of breast cancer is complex and multifactorial and may include environmental risk factors. Breast cancer etiology and exposure to xenobiotic compounds, diet, electromagnetic fields, and lifestyle have been the subject of numerous scientific inquiries, but research has yielded inconsistent results. Biomonitoring has been used to explore associations between breast cancer and levels of environmental chemicals in the breast. Research using breast tissues and fluids to cast light on the etiology of breast cancer is, for the most part, predicated on the assumption that the tissue or fluid samples either contain measurable traces of the environmental agent(s) associated with the cancer or that they retain biological changes that are biomarkers of such exposure or precursors of carcinogenic effect. In this paper, we review breast cancer etiology research utilizing breast biomonitoring. We first provide a brief synopsis of the current state of understanding of associations between exposure to environmental chemicals and breast cancer etiology. We then describe the published breast cancer research on tissues and fluids, which have been used for biomonitoring, specifically human milk and its components, malignant and benign breast tissue, nipple aspirate fluid (NAF) and breast cyst fluid. We conclude with a discussion on recommendations for biomonitoring of breast tissues and fluids in future breast cancer etiology research. Both human milk and NAF fluids, and the cells contained therein, hold promise for future biomonitoring research into breast cancer etiology, but must be conducted with carefully delineated hypotheses and a scientifically supportable epidemiological approach.

  12. A Comparative Study on Digital Mammography and Ultrasonography in Diagnosis of Breast Ductal Carcinoma%乳腺导管内癌数字化摄影与超声诊断的对比研究

    Institute of Scientific and Technical Information of China (English)

    徐向红; 赵玉年; 王慧华

    2012-01-01

    Objective To investigate the value of digital mammography and ultrasonography in diagnosis of breast ductal carcinoma. Methods 53 cases of ductal carcinoma were retrospectively analyzed. The digital mammography and ultrasonography were performed in all cases. The diagnosis of digital mammography and ultrasonography was divided into probably malignant, indeterminate , probably benign, and negative. According to surgical and histopathological outcomes, a comparative study on the value of digital mammo-graphy and ultrasonography was performed. Results There are 36 cases and 33 cases of probably malignant ,4 cases and 5 cases of indeterminate,7 cases and 10 cases of of probably benign,6 cases and 5 cases of negative diagnosed by digital mammography and ultrasonography respectively. The accuracy of digital mammography and ultrasonography were 67. 9%( 36/53 ) and 62. 3% ( 33/53 ) respectively. The accuracy of digital mammography associated with ultrasonography was 88. 7%( 47/53 ). Conclusion Digital mammography and ultrasonography are valuable in the diagnosis of breast ductal carcinoma. The diagnostic accuracycan be improved by the combination of the two methods.%目的 探讨数字化摄影与超声检查对乳腺导管内癌的诊断价值.方法 回顾性分析53例乳腺导管内癌病例,所有病例都接受了数字化摄影及超声检查.数字化摄影和超声诊断分为可能恶性、性质待定、可能良性和阴性.对照手术和病理组织学检查结果,比较数字化摄影和超声检查的价值.结果 数字化摄影和超声分别诊断可能恶性36例和33例,性质待定4例和5例,可能良性7例和10例,阴性6例和5例.数字化摄影和超声诊断的准确性分别是67.9%(36/53)和62.3%(33/53).数字化摄影结合超声诊断的准确性是88.7%(47/53).结论 数字化摄影和超声诊断可用于乳腺导管内癌的诊断,联合应用可提高诊断的准确性.

  13. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2...

  14. Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures

    Directory of Open Access Journals (Sweden)

    Härkönen Pirkko

    2006-10-01

    Full Text Available Abstract Background Human breast tissue undergoes phases of proliferation, differentiation and regression regulated by changes of the levels of circulating sex hormones during the menstrual cycle or aging. Ovarian hormones also likely play a key role in the etiology and biology of breast cancer. Reports concerning the proliferative effects of steroid hormones on the normal epithelium of human breast have been conflicting. Some studies have shown that steroid hormones may predispose breast epithelial cells to malignant changes by stimulating their proliferation, which is known to be regulated tightly by stromal cells. The aim of this study was to investigate the effects of 17β-estradiol and medroxyprogesterone acetate on proliferation, apoptosis, expression of differentiation markers and steroid hormone receptors in breast epithelium using an in vitro model of freshly isolated human breast tissue, in which a proper interaction of breast epithelium and stroma has been maintained. Methods Human breast tissues were obtained from women undergoing surgery for breast tumours. Peritumoral tissues were excised and explants were cultured for 3 weeks in medium supplemented with E2 or MPA or with E2+MPA. Endpoints included histopathological, histomorphometric and immunohistochemical assessment of the breast explants. Results Culture of breast explants for 14 or 21 days with steroid hormones increased proliferative activity and the thickness of acinar and ductal epithelium. E2-treatment led to hyperplastic epithelial morphology, MPA to hypersecretory single-layered epithelium and E2+MPA to multilayered but organised epithelium. The proliferative response to E2 in comparison to control (p was more pronounced than to MPA (p or E2+MPA (p at 7 and 14 days for Ki-67 and PCNA. E2 treatment also decreased the proportion of apoptotic cells after 7 (p and 14 (p days. In addition, the relative number of ERα, ERβ and PR positive epithelial cells was decreased by all

  15. 乳脂肪球因子8在乳腺浸润性导管癌中的表达及临床意义%Clinical significance and expression of milk fat globule-epidermal growth factor 8 in invasive ductal breast cancer

    Institute of Scientific and Technical Information of China (English)

    李杰宝; 张家衡

    2015-01-01

    Objective To study the clinical significance and expression of milk fat globule-epidermal growth factor 8 (MFG-E8) in invasive ductal carcinoma of breast.Methods Immunohistochemical study for MFG-E8 was performed on paraffin sections of 30 cases of breast cancer tissues.The correlation of MFG-E8 expression to clinicopathologic features of breast cancer was analyzed.Results The intensive positive rate of MFG-E8 in breast cancer was 83.3% (25/30),which was significantly higher than that in normal breast tissues (P < 0.01).The intensive expression of MFG-E8 was positively correlated to histologic grade (P < 0.01),but not to tumor size,clinical stage,lymphnode metastasis,the expression of progesterone receptor (PR) arid human epidermalgrowth factor receptor-2 (Her-2,P > 0.05).Positive correlation was observed between the expression of MFG-E8 and estrogen receptor (ER) in breast cancer (P < 0.05).Conclusion The intensive expression of MFG-E8 was found in invasive ductal carcinoma of breast.The high expression of MFG-E8 may act as a prognosis factor for brest cancer patients and provide evidents to targeted therapy of breast cancer.%目的 探讨乳脂肪球因子8(MFG-E8)蛋白在乳腺浸润性导管癌组织中的表达及意义.方法 应用免疫组织化学法[链霉菌抗生物素蛋白-过氧化物酶(SP)法]检测30例乳腺浸润性导管癌组织中MFG-E8蛋白的表达,并结合患者的临床病理资料分析其临床意义.结果 乳腺浸润性导管癌组织中的MFG-E8的强阳性表达率为83.3%(25/30),高于癌旁乳腺组织的3.3%(1/30,P <0.01);MFG-E8的阳性表达与乳腺癌的组织学分级及雌激素受体(ER)密切相关(P<0.01),而与肿瘤大小、淋巴结转移、孕激素受体(PR)、人类表皮生长因子受体2(Her-2)及临床分期无明显相关(P >0.05);MFG-E8和ER在乳腺癌组织中的表达呈正相关(P<0.05).结论 乳腺浸润性导管癌组织中MFG-E8高表达,其高表达可预测乳腺癌的预后.

  16. Neogenin expression may be inversely correlated to the tumorigenicity of human breast cancer

    Directory of Open Access Journals (Sweden)

    Kim Sung-Won

    2005-12-01

    Full Text Available Abstract Background Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. Methods To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong by a single well-trained blinded pathologist and statistically analyzed. Results The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8 of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46 of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p Conclusion Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation.

  17. Diagnostic value comparison of ultrasonography and mammography in breast infiltrating ductal carcinoma%超声与钼靶X线对浸润性导管癌临床诊断价值的比较

    Institute of Scientific and Technical Information of China (English)

    胡波; 周碧华; 庞彩霞; 章瑜

    2013-01-01

    目的:对比超声与钼靶X线检查在乳腺浸润性导管癌中的诊断价值.方法:对420例乳腺肿块患者按绝经前后分两组比较超声及钼靶X线检查对乳腺浸润性导管癌的诊断准确性,并对病理证实122例乳腺浸润性导管癌的超声及钼靶X线征象进行对比分析.结果:绝经前组超声符合率89.7%,钼靶X线诊断符合率74.8%;绝经后组超声的诊断符合率为89.7%,钼靶X线诊断符合率为89.1%.绝经前超声诊断乳腺浸润性导管癌比钼靶X线的诊断符合率高 (P<0.05),绝经后两者诊断符合率差异无统计学意义(P>0.05).绝经前乳腺浸润性导管癌患者中的超声检查对乳腺肿块影、钙化灶检出率均高于钼靶X线(P<0.05).结论:超声与钼靶X线对绝经前、后浸润性导管癌均有较高诊断价值,乳腺超声成像对绝经前浸润性导管癌患者的诊断价值更大.%Objective:To evaluate the value of ultrasonography and mammography in diagnosis of breast infiltrating ductal cancer.Methods:420 cases of mammary tumor patients were analyzed retrospectively.They were divided into premenopausal group and postmenopausal group.Pathologic result were chosen to be gold standard.The diagnostic accuracy of mammography and ultrasound was compared and then mammography and ultrasound signs were comparative analysis in the pathology confirmed premenopausal sixty cases of infiltrating ductal carcinoma patients.Results:In the group of premenopausal:the diagnosis coincidence rate of ultrasonography was 89.7%,the diagnosis coincidence rate of mammography was 74.8%.In the group of postmenopausal:the diagnosis coincidence rate of ultrasonography was 89.7%,the diagnosis coincidence rate of mammography was 89.1%.The diagnosis coincidence rates of ultrasonograph were higher than those of mammography in the group of premenopausal (P < 0.05).The diagnosis coincidence rate was no significant difference in the group of postmenopausal

  18. Chemical Biomarkers of Human Breast Milk Pollution

    Directory of Open Access Journals (Sweden)

    Benedetta Marchi

    2008-01-01

    Full Text Available Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics.In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed.In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

  19. Excretion of drugs in human breast milk

    Energy Technology Data Exchange (ETDEWEB)

    Welch, R.M.; Findlay, J.W.

    1981-01-01

    The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.

  20. Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

    Science.gov (United States)

    2017-07-28

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  1. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    Science.gov (United States)

    2017-04-12

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  2. Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones

    Directory of Open Access Journals (Sweden)

    Cláudio Jorge Maia

    2016-06-01

    Full Text Available Oligoadenylate synthetase 1 (OAS1 is an interferon-induced protein characterised by its capacity to catalyse the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A. The 2-5A binds to a latent Ribonuclease L (RNase L, which subsequently dimerises into its active form and may play an important role in the control of cell growth, differentiation and apoptosis. Previously, our research group identified OAS1 as a differentially-expressed gene in breast and prostate cancer cell lines when compared to normal cells. This study evaluates: i the expression of OAS1 in human breast and prostate cancer specimens; and ii the effect of sex steroid hormones in regulating the expression of OAS1 in breast (MCF-7 and prostate (LNCaP cancer cell lines. The obtained results showed that OAS1 expression was down-regulated in human infiltrative ductal carcinoma of breast, adenocarcinoma of prostate, and benign prostate hyperplasia, both at mRNA and protein level. In addition, OAS1 expression was negatively correlated with the progression of breast and prostate cancer. With regards to the regulation of OAS1 gene, it was demonstrated that 17β-estradiol (E2 down-regulates OAS1 gene in MCF-7 cell lines, an effect that seems to be dependent on the activation of oestrogen receptor (ER. On the other hand, 5α-dihydrotestosterone (DHT treatment showed no effect on the expression of OAS1 in LNCaP cell lines. The lower levels of OAS1 in breast and prostate cancer cases indicated that the OAS1/RNaseL apoptotic pathway may be compromised in breast and prostate tumours. Moreover, the present findings suggested that this effect may be enhanced by oestrogen in ER-positive breast cancers.

  3. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  4. Effect of CCR7, CXCR4 and VEGF-C on the lymph node metastasis of human pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Guo, Jinghui; Lou, Wenhui; Ji, Yuan; Zhang, Shuncai

    2013-05-01

    The aim of the present study was to investigate the association between the expression of chemokine receptors CCR7 and CXCR4 and vascular endothelial growth factor (VEGF)-C and the lymph node metastasis of pancreatic ductal adenocarcinoma (PDAC). The mRNA transcription levels of CCR7, CXCR4 and VEGF-C were measured in 24 specimens by real-time reverse transcription (RT)-PCR, while the protein expression levels were measured in 65 specimens by immuohistochemistry. Professional software for pathological image manipulation (Image Pro Plus 6.0) was used to quantitate the results of the immunohistochemical staining. The mRNA and protein expression levels of CCR7, CXCR4 and VEGF-C were all significantly higher in the cancer samples compared with those in the adjacent normal tissue. The CCR7 and VEGF-C mRNA and protein expression levels were significantly higher in the patients with cancer types exhibiting lymph node metastasis and an advanced International Union Against Cancer (UICC) stage (PCCR7 expression (PCCR7 and VEGF-C (P0.05), however the strong positive expression of CCR7 and VEGF-C was significantly associated with the lymph node metastasis of PDAC.

  5. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    Science.gov (United States)

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong

    2017-01-01

    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.

  6. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  7. Molecular Insights on the Transition of Non-invasive DCIS to Invasive ductal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dihua YU

    2009-01-01

    @@ More than 90% of breast cancer-related deaths are caused by metastasis not primary tumor. To effectively reduce cancer mortality, it is extremely im-portant to predict the risk of, and to intervene in, the critical transition from non-invasive ductal carcinoma in situ (DCIS) to life-threatening invasive ductal carcinoma (IDC).

  8. Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants.

    Science.gov (United States)

    Wang, Kai-Hung; Kao, An-Pei; Chang, Chia-Cheng; Lin, Ta-Chin; Kuo, Tsung-Cheng

    2016-01-01

    We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC) from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate) is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40) of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

  9. Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants

    Directory of Open Access Journals (Sweden)

    Kai-Hung Wang

    2016-01-01

    Full Text Available We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate is a better medium to grow human breast epithelial cells. The results clearly show that the K-NAC medium is a superior medium for prolonged growth (cumulative population doubling levels ranged from 30 to 40 of normal breast epithelial cells that expressed stem cell phenotypes. The characteristics of these mammary stem cells include deficiency in gap junctional intercellular communication, expression of Oct-4, and the ability to differentiate into basal epithelial cells and to form organoid showing mammary ductal and terminal end bud-like structures. Thus, this new method of growing Type I HBECs will be very useful in future studies of mammary development, breast carcinogenesis, chemoprevention, and cancer therapy.

  10. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    Science.gov (United States)

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

  11. The expression patterns and correlations of claudin-6, methy-CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl-histone H3 and acetyl-histone H4 and their clinicopathological significance in breast invasive ductal carcinomas

    Directory of Open Access Journals (Sweden)

    Xu Xiaoming

    2012-03-01

    Full Text Available Abstract Background Claudin-6 is a candidate tumor suppressor gene in breast cancer, and has been shown to be regulated by DNA methylation and histone modification in breast cancer lines. However, the expression of claudin-6 in breast invasive ductal carcinomas and correlation with clinical behavior or expression of other markers is unclear. We considered that the expression pattern of claudin-6 might be related to the expression of DNA methylation associated proteins (methyl-CpG binding protein 2 (MeCP2 and DNA methyltransferase 1 (DNMT1 and histone modification associated proteins (histone deacetylase 1 (HDAC1, acetyl-histone H3 (H3Ac and acetyl- histone H4 (H4Ac. Methods We have investigated the expression of claudin-6, MeCP2, HDAC1, H3Ac and H4Ac in 100 breast invasive ductal carcinoma tissues and 22 mammary gland fibroadenoma tissues using immunohistochemistry. Results Claudin-6 protein expression was reduced in breast invasive ductal carcinomas (P P P = 0.001, HDAC1 (P P = 0.004 expressions was increased. Claudin-6 expression was inversely correlated with lymph node metastasis (P = 0.021. Increased expression of HDAC1 was correlated with histological grade (P P = 0.004, clinical stage (P = 0.007 and lymph node metastasis (P = 0.001. H3Ac expression was associated with tumor size (P = 0.044 and clinical stage of cancers (P = 0.034. MeCP2, DNMT1 and H4Ac expression levels did not correlate with any of the tested clinicopathological parameters (P > 0.05. We identified a positive correlation between MeCP2 protein expression and H3Ac and H4Ac protein expression. Conclusions Our results show that claudin-6 protein is significantly down-regulated in breast invasive ductal carcinomas and is an important correlate with lymphatic metastasis, but claudin-6 down-regulation was not correlated with upregulation of the methylation associated proteins (MeCP2, DNMT1 or histone modification associated proteins (HDAC1, H3Ac, H4Ac. Interestingly, the

  12. Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma

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    Dietl Johannes

    2007-10-01

    Full Text Available Abstract Background LIM and SH3 protein 1 (LASP-1, initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration, which was reported to be overexpressed in 8–12 % of human breast cancers and thought to be exclusively located in cytoplasm. Methods In the present work we analyzed the cellular and histological expression pattern of LASP-1 and its involvement in biological behavior of human breast cancer through correlation with standard clinicopathological parameters and expression of c-erbB2 (HER-2/neu, estrogen- (ER and progesterone-receptors (PR. For this purpose immunohistochemical staining intensity and percentage of stained cells were semi-quantitatively rated to define a LASP-1 immunoreactive score (LASP-1-IRS. LASP-1-IRS was determined in 83 cases of invasive ductal breast carcinomas, 25 ductal carcinomas in situ (DCIS and 18 fibroadenomas. Cellular LASP-1 distribution and expression pattern was visualized by immunofluorescence and confocal microscopy and assessed through separate Western blots of nuclear and cytosol preparations of BT-20, MCF-7, MDA-MB231, and ZR-75/1 breast cancer cells. Results Statistical analysis revealed that the resulting LASP-1-IRS was significantly higher in invasive carcinomas compared to fibroadenomas (p = 0.0176. Strong cytoplasmatic expression of LASP-1 was detected in 55.4 % of the invasive carcinomas, which correlated significantly with nuclear LASP-1-positivity (p = 0.0014, increased tumor size (p = 0.0159 and rate of nodal-positivity (p = 0.0066. However, levels of LASP-1 expression did not correlate with average age at time point of diagnosis, histological tumor grading, c-erbB2-, ER- or PR-expression. Increased nuclear localization and cytosolic expression of LASP-1 was found in breast cancer with higher tumor stage as well as in rapidly proliferating epidermal basal cells. Confocal microscopy and separate Western blots of cytosolic and

  13. 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

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    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

  14. Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

    Science.gov (United States)

    Ben-Batalla, Isabel; Seoane, Samuel; Garcia-Caballero, Tomas; Gallego, Rosalia; Macia, Manuel; Gonzalez, Luis O.; Vizoso, Francisco; Perez-Fernandez, Roman

    2010-01-01

    The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target. PMID:21060149

  15. Lactate dehydrogenase-B is silenced by promoter methylation in a high frequency of human breast cancers.

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    Nicola J Brown

    Full Text Available OBJECTIVE: Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. EXPERIMENTAL DESIGN: Lactate Dehydrogenase (LDH isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. RESULTS: Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/25 cases of breast cancer tissues, but not in 5/5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained, was seen in 23/26 (88% breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O(2, for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002, and T-47D cells (2.9 fold, p = 0.009, but not in MDA-MB-436 (-0.9 fold, p = 0.229, or MCF10AT (1.2 fold, p = 0.09 cells. CONCLUSIONS: Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia.

  16. Ductal carcinoma in situ diagnosed using an ultrasound-guided 14-gauge core needle biopsy of breast masses: can underestimation be predicted preoperatively?

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    Sung Hee Park

    2014-04-01

    Conclusion: We found a 30.4% rate of DCIS underestimation in breast masses based on a US-14G-CNB. The presence of abnormal lymph nodes as detected on axillary ultrasound may be useful to preoperatively predict underestimation.

  17. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells.

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    Marica Vaapil

    Full Text Available INTRODUCTION: Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis. METHODS: Normal human primary breast epithelial cells and immortalized non-malignant mammary epithelial MCF-10A cells were grown in a three-dimensional overlay culture on laminin-rich extracellular matrix for up to 21 days at normoxic or hypoxic conditions. Acinar morphogenesis and expression of markers of epithelial differentiation and cell polarization were analyzed by immunofluorescence, immunohistochemistry, qPCR and immunoblot. RESULTS: In large ductal carcinoma in situ patient-specimens, we find that epithelial cells with high HIF-1α levels and multiple cell layers away from the vasculature are immature compared to well-oxygenated cells. We show that hypoxic conditions impaired acinar morphogenesis of primary and immortalized breast epithelial cells grown ex vivo on laminin-rich matrix. Normoxic cultures formed polarized acini-like spheres with the anticipated distribution of marker proteins associated with mammary epithelial polarization e.g. α6-integrin, laminin 5 and Human Milk Fat Globule/MUC1. At hypoxia, cells were not polarized and the sub-cellular distribution pattern of the marker proteins rather resembled that reported in vivo in breast cancer. The hypoxic cells remained in a mitotic state, whereas proliferation ceased with acinar morphogenesis at normoxia. We found induced expression of the differentiation repressor ID1 in the undifferentiated hypoxic MCF-10A cell structures. Acinar

  18. 环氧化酶2和血管内皮生长因子在乳腺浸润性导管癌中的表达及其临床意义%Expressions of COX-2 and VEGF in breast invasive ductal carcinoma and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    李伟; 熊正文; 李宏伟; 胡海霞; 黄勇; 张华东

    2011-01-01

    Objective To investigate the mRNA and protein expressions of cyclooxygenase-2 ( COX-2 ) and vascular endothelial growth factor ( VEGF ) in breast invasive ductal carcinoma and analyze their relationship with clinicopathological characteristics. Methods The mRNA and protein expressions of COX-2 and VEGF were detected in 70 cases of breast invasive ductal carcinoma and 30 cases of breast fibroadenoma using in situ hybridization and immunohistochemical SP method. The enumeration data were analyzed by x2 test. The correlation analysis was performed by Spearman test. Results The positive rate of COX-2 mRNA in breast invasive ductal carcinoma (74. 2% , 52/70) was significantly higher than in breast fibroadenoma (30. 0% , 9/30 ) (x2 = 17. 31, P = 0. 00). The positive rate of COX-2 protein in breast invasive ductal carcinoma (72. 8% , 51/70) was significantly higher than that in breast fibroadenoma (23. 3% , 7/30) (x2 = 21. 14, P = 0. 00). In breast invasive ductal carcinoma, COX-2 mRNA and protein expressions were related to lymphatic metastasis (x2 =7. 54, P=0. 00;x2=6. 36,P = 0. 01) ,but not related to age, tumor size and histopathological grade. The positive rate of VEGF mRNA in breast invasive ductal carcinoma (71. 4% , 50/70) was significantly higher than that in breast fibroadenoma (33.3% , 10/30) (x2 = 12. 70,P = 0. 00). The positive rate of VEGF protein in breast invasive ductal carcinoma (65. 7% , 46/70) was significantly higher than that in breast fibroadenoma ( 26. 7% , 8/30 ) ( x2 = 12. 89, P = 0. 00 ). The expression of VEGF mRNA in breast invasive ductal carcinoma was related to lymphatic metastasis (x2 =8. 33, P=0.00), but not related to age, tumor size and histopathological grade (P>0.05). VEGF protein expression was related to lymphatic metastasis and histopathological grade (P 0. 05 ). The mRNA and protein expressions of VEGF were positively correlated with the mRNA and protein expressions of COX-2 in breast invasive ductal carcinoma ( r = 0. 64, P = 0

  19. Estrogen Receptor Mutants/Variants in Human Breast Cancer.

    Science.gov (United States)

    1995-12-01

    Human breast tissues and cell lines. Normal breast tissues were obtained from reduction mammoplastv surgical specimens collected at the Necker Hospital ...mammoplasty specimens collected at the laboratory of F. Kuttenn, Necker Hospital , France (4 cases) and at the Manitoba Breast Tumor Bank (4 cases). Human...method for the identification of mutations and polymorphisms in the gene for glycoprotein IIIa. Blood 1993, 8:2281-2288 2 Ikonen E, Aula P, Gron K

  20. KeraStat Skin Therapy in Treating Radiation Dermatitis in Patients With Newly Diagnosed Stage 0-IIIA Breast Cancer

    Science.gov (United States)

    2017-05-25

    Ductal Breast Carcinoma in Situ; Skin Reactions Secondary to Radiation Therapy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  1. A rare presentation of mammary Paget′s disease involving the entire breast in the absence of any underlying ductal malignancy

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    Shuchi Bansal

    2013-01-01

    Full Text Available Paget′s disease of the breast is an uncommon form of breast cancer presenting as an eczematous eruption over the nipple and/or areola. The diagnosis remains elusive with varied presentations, mimicking many benign skin diseases, the awareness of which is indispensable for diagnosis and minimizing morbidity. Most of the cases have an associated malignancy of the underlying breast tissue. There have been very few reports wherein the disease has occurred independent of any underlying malignancy. Since, the initial presentation is limited to skin; it is the dermatologist who plays a key role in making a diagnosis, thus, facilitating proper management. We report a rare presentation of mammary Paget′s disease with a wide cutaneous spread probably attributed to a significantly delayed diagnosis without any associated underlying malignancy.

  2. A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression.

    Science.gov (United States)

    Streckfus, Charles F; Bigler, Lenora

    2016-08-01

    The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care.

  3. 3-D reconstruction and virtual ductoscopy of high-grade ductal carcinoma in situ of the breast with casting type calcifications using refraction-based X-ray CT.

    Science.gov (United States)

    Ichihara, Shu; Ando, Masami; Maksimenko, Anton; Yuasa, Tetsuya; Sugiyama, Hiroshi; Hashimoto, Eiko; Yamasaki, Katsuhito; Mori, Kensaku; Arai, Yoshinori; Endo, Tokiko

    2008-01-01

    Stereomicroscopic observations of thick sections, or three-dimensional (3-D) reconstructions from serial sections, have provided insights into histopathology. However, they generally require time-consuming and laborious procedures. Recently, we have developed a new algorithm for refraction-based X-ray computed tomography (CT). The aim of this study is to apply this emerging technology to visualize the 3-D structure of a high-grade ductal carcinomas in situ (DCIS) of the breast. The high-resolution two-dimensional images of the refraction-based CT were validated by comparing them with the sequential histological sections. Without adding any contrast medium, the new CT showed strong contrast and was able to depict the non-calcified fine structures such as duct walls and intraductal carcinoma itself, both of which were barely visible in a conventional absorption-based CT. 3-D reconstruction and virtual endoscopy revealed that the high-grade DCIS was located within the dichotomatous branches of the ducts. Multiple calcifications occurred in the necrotic core of the continuous DCIS, resulting in linear and branching (casting type) calcifications, a hallmark of high-grade DCIS on mammograms. In conclusion, refraction-based X-ray CT approaches the low-power light microscopic view of the histological sections. It provides high quality slice data for 3-D reconstruction and virtual ductosocpy.

  4. Comparison of Nuclear Accumulation of p53 Protein with Mutations in the p53 Gene of Human Breast Cancer Tissues

    Institute of Scientific and Technical Information of China (English)

    王萱仪; 查小明; 武正炎; 范萍

    2001-01-01

    Objective The objective was to compare nuclear accumulation of p53 protein with mutations in the p53 gene on the tissues of human breast cancer. Methods Fifty-four invasive ductal carcinomas of breast were analyzed by the method of polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) silver stain and strep-avidin-biotin-peroxidase complex (SABC) immunohistochemistry. Results A statistically significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (P<0.01). 22 tumors that demonstrated p53 gene mutations showed nuclear accumulation of p53 protein, while only 9 (28%) showed nuclear accumulation of p53 protein in 32 tumors without p53 gene mutations. Both p53 mutation protein and p53 gene mutations were prevalent in steroid and progesterone receptors negative tumors (P<0.05). A statistically significant association was found between the nuclear accumulation of p53 protein and lymph node invasion (P<0.05), and between p53 gene mutations and lymph node invasion (P<0.05). p53 abnormalities might be associated with an aggressive phenotype in breast cancer. Conclusion The immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in breast cancer tissues, and that this method is useful for rapid screening of p53 abnormalities. However, in order to avoid false positive reaction, the p53 gene mutations should be determined in cases slightly positive for p53 nuclear protein.

  5. Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice.

    Science.gov (United States)

    Nemec, Matthew J; Kim, Hyemee; Marciante, Alexandria B; Barnes, Ryan C; Hendrick, Erik D; Bisson, William H; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2017-03-01

    The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Is sentinel lymph node biopsy necessary for the patients diagnosed with breast ductal carcinoma in situ using core needle biopsy or vacuum-assisted biopsy as the initial diagnostic method?

    Institute of Scientific and Technical Information of China (English)

    Xiaoyi Zhang; Rui Wang; Zhiyong Wu; Xueqing Jiang

    2014-01-01

    Objective:Axil ary lymph node status is one of the most important prognostic indicator of survival for breast cancer, especial y in ductal carcinoma in situ (DCIS). The purpose of this study was to investigate whether sentinel lymph node biopsy (SLNB) should be performed in patients with an initial diagnosis of DCIS. Methods:A retrospective study was performed of 124 patients with an initial diagnosis of DCIS between March 2000 and June 2014. The patients were treated with either SLNB or axil ary node dissection during the surgery, and we compared the clinicopathologic characteristics, image features, and immunohistochemical results. Results:Eighty-two patients (66.1%) had pure DCIS and 25 (20.2%) had DCIS with microinvasion (DCISM), 17 (13.7%) updated to invasive breast cancer (IBC). 115 patients (92.7%) underwent SLNB, among them, 70 patients (56.5%) underwent axil ary node dissection. 3 of 115 patients (2.6%) had a positive sentinel lymph node, only 1 (1.4%) of 70 patients had axil ary lymph node metastasis, in 84 patients (66.7%) who were diagnosed DCIS by core needle biopsy (CNB) and vacuum-assisted biopsy (VAB). 26 patients (31.0%) were upstaged into IBC or DCISM in the final histological diagnosis. The statistical y significant factors predictive of underestimation were large tumor size, microcalci-fications, comedo necrosis, positive Her-2 status, negative estrogen receptor status. Conclusion:The metastasis of sentinel lymph nodes in pure DCIS is very low, but the underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS is an usual incident, especial y in the cases when DCIS is diagnosed by CNB or VAB. Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with large tumor sizes, microcalcifications, comedo necrosis, positive Her-2 status, negative ER status are more likely to be DCISM and IBC in final diagnosis. SLNB should be performed in this part of patients.

  7. Imaging of human breast tissue using polarization sensitive optical coherence tomography

    Science.gov (United States)

    Verma, Y.; Gautam, M.; Divakar Rao, K.; Swami, M. K.; Gupta, P. K.

    2011-12-01

    We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.

  8. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  9. Prognostic differences of World Health Organization - assessed mitotic activity index and mitotic impression by quick scanning in invasive ductal breast cancer patients younger than 55 years

    NARCIS (Netherlands)

    Skaland, Ivar; van Diest, Paul J.; Janssen, Emiel A. M.; Gudlaugsson, Einar; Baak, Jan P. A.

    2008-01-01

    The proliferation marker mitotic activity index is the strongest prognostic indicator in lymph node-negative breast cancer. The World Health Organization (WHO) 2003-defined procedure for determining WHO-mitotic activity index is often replaced by a quick scan mitotic impression. We evaluated the pro

  10. Expressão da aromatase em carcinomas de mama ductais invasivo e in situ presentes na mesma mama Aromatase expression in invasive and in situ ductal carcinoma present in the same breast

    Directory of Open Access Journals (Sweden)

    Vilmar Marques de Oliveira

    2009-01-01

    Full Text Available OBJETIVO: Avaliar expressão da enzima aromatase nos carcinomas de mama ductais invasivos (CDI, in situ (CDIS, no epitélio e estromas adjacentes. MÉTODOS: Foram avaliados 45 espécimes cirúrgicos provenientes de mastectomias e quadrantectomias com CDI e CDIS concomitantes de pacientes com estadios clínicos I e II. A análise da expressão da enzima aromatase foi realizada por meio de anticorpos policlonais antiaromatase e categorização das amostras de acordo com intensidade e número de células coradas. RESULTADOS: Nos 45 casos de CDI a expressão da aromatase foi positiva em 32 espécimes (71% e negativa em 13 (29%. Nos casos de CDIS, a positividade foi idêntica à observada no CDI, mostrando correlação positiva. No epitélio normal constatou-se expressão positiva em 19 casos (42,2% e negativa nos outros 26 (57,8%, mostrando correlação positiva estatisticamente (pOBJECTIVE: to evaluate the expression of aromatase in simultaneously invasive ductal carcinoma (IDC and ductal carcinoma in situ (DCIS. METHODS: forty-five surgical samples were obtained from mastectomy and quadrantectomy with simultaneous IDC and DCIS of stage I and II patients. Aromatase was evaluated using antibodies anti-aromatase and the samples classified in accordance with the number and intensity of stained cells. RESULTS: Aromatase was expressed positively in 32(71% and negatively in 13(29% of the cases in the IDC. The same results were obtained in the DCIS showing a perfect positive correlation. In the normal epithelium,aromatase was positive in 19(42.2% and negative in 26 (57.8% and a positive correlation, statistically significant was obtained when compared with IDC and DCIS(p<0.01. Concerning the normal stroma, positivity was only 7 (15.5% showing no correlation with aromatase expression. Aromatase was positive in 36(80% of the tumor stroma and this result was statistically significant as in the IDC and DCIS. Comparing results of aromatase expression with

  11. Real-time growth kinetics measuring hormone mimicry for ToxCast chemicals in T-47D human ductal carcinoma cells.

    Science.gov (United States)

    Rotroff, Daniel M; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Reif, David M; Richard, Ann M; Sipes, Nisha S; Abassi, Yama A; Jin, Can; Stampfl, Melinda; Judson, Richard S

    2013-07-15

    High-throughput screening (HTS) assays capable of profiling thousands of environmentally relevant chemicals for in vitro biological activity provide useful information on the potential for disrupting endocrine pathways. Disruption of the estrogen signaling pathway has been implicated in a variety of adverse health effects including impaired development, reproduction, and carcinogenesis. The estrogen-responsive human mammary ductal carcinoma cell line T-47D was exposed to 1815 ToxCast chemicals comprising pesticides, industrial chemicals, pharmaceuticals, personal care products, cosmetics, food ingredients, and other chemicals with known or suspected human exposure potential. Cell growth kinetics were evaluated using real-time cell electronic sensing. T-47D cells were exposed to eight concentrations (0.006-100 μM), and measurements of cellular impedance were repeatedly recorded for 105 h. Chemical effects were evaluated based on potency (concentration at which response occurs) and efficacy (extent of response). A linear growth response was observed in response to prototypical estrogen receptor agonists (17β-estradiol, genistein, bisphenol A, nonylphenol, and 4-tert-octylphenol). Several compounds, including bisphenol A and genistein, induced cell growth comparable in efficacy to that of 17β-estradiol, but with decreased potency. Progestins, androgens, and corticosteroids invoked a biphasic growth response indicative of changes in cell number or cell morphology. Results from this cell growth assay were compared with results from additional estrogen receptor (ER) binding and transactivation assays. Chemicals detected as active in both the cell growth and ER receptor binding assays demonstrated potencies highly correlated with two ER transactivation assays (r = 0.72; r = 0.70). While ER binding assays detected chemicals that were highly potent or efficacious in the T-47D cell growth and transactivation assays, the binding assays lacked sensitivity in detecting

  12. Gene transcriptional networks integrate microenvironmental signals in human breast cancer.

    Science.gov (United States)

    Xu, Ren; Mao, Jian-Hua

    2011-04-01

    A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell-cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.

  13. Lubricin in human breast tissue expander capsules.

    Science.gov (United States)

    Cheriyan, Thomas; Guo, Lifei; Orgill, Dennis P; Padera, Robert F; Schmid, Thomas M; Spector, Myron

    2012-10-01

    Capsular contraction is the most common complication of breast reconstruction surgery. While presence of the contractile protein alpha smooth muscle actin (α-SMA) is considered among the causes of capsular contraction, the exact etiology and pathophysiology is not fully understood. The objective of this study was to investigate the possible role of lubricin in capsular formation and contraction by determining the presence and distribution of the lubricating protein lubricin in human breast tissue expander capsules. Related aims were to evaluate select histopathologic features of the capsules, and the percentage of cells expressing α-SMA, which reflects the myofibroblast phenotype. Capsules from tissue expanders were obtained from eight patients. Lubricin, at the tissue-implant interface, in the extracellular matrix, and in cells, and α-SMA-containing cells were evaluated immunohistochemically. The notable finding was that lubricin was identified in all tissue expander capsules: as a discrete layer at the tissue-implant interface, extracellular, and intracellular. There was a greater amount of lubricin in the extracellular matrix in the intimal-subintimal zone when compared with the tissue away from the implant. Varying degrees of synovial metaplasia were seen at the tissue-implant interface. α-SMA-containing cells were also seen in all but one patient. The findings might help us better understand factors involved in capsule formation.

  14. Expression of stem cell key transfer factor FoxD3 in breast invasive ductal carcinomas%乳腺浸润性导管癌中干细胞关键转录因子FoxD3的表达

    Institute of Scientific and Technical Information of China (English)

    印永祥; 赵华; 王嘉园; 陈道桢; 高琼; 张晔

    2012-01-01

    目的 探讨干细胞关键转录因子FoxD3在乳腺浸润性导管癌(invasive duct carcinomas,IDC)组织中的表达.方法 采用免疫组化MaxVision法检测FoxD3、HER-2、Ki-67、ER和PR在79例乳腺IDC组织中的表达,HER-2结果附加荧光原位杂交(fluorescence in situ hybridization,FISH)确诊.结果 FoxD3蛋白表达与患者年龄、病理分级、临床分期、HER-2状态和激素状态无明显相关(P>0.05).与淋巴结未转移组相比,淋巴结转移组低表达FoxD3蛋白(P 0. 05 ). The expression of FoxD3 and Ki-67 was significantly increased in invasive ductal breast cancer without lymphatic metastasis compared to that in invasive ductal breast cancer with lymphatic metastasis ( P 0. 05 ). Conclusion The decreasing expression of FoxD3 may play an important role in the metastasis of invasive breast cancer. FoxD3 may provide a basis for the development of a novel therapeutic target in breast cancer.

  15. 乳腺MRI与乳腺X线检查诊断导管原立癌的敏感度研究%MRI outstands mammogram in sensitivity of breast ductal carcinoma in situ : an analysis of 122 cases

    Institute of Scientific and Technical Information of China (English)

    郁骐襄; 陈小松; 吴佳毅; 韩宝三; 何建蓉; 朱丽; 陈伟国; 李亚芬; 谭令

    2013-01-01

    Objectives To compare the sensitivity of mammogram and breast dedicated MRI in detecting ductal carcinoma in situ with microinvaion (DCIS-MI) and ductal carcinoma in situ (DCIS) lesions,and to further investigate the independent predictive factors of mammogram and MRI sensitivity.Methods From August 2009 to November 2011,122 consecutive confirmed breast cancer patients who had received operations were recruited for this clinical research.These patients were divided into two groups including DCIS (72 cases) and DCIS-MI (50 cases) based on pathologic reports.All the patients were female,with mean ages of 52.6 years and 54.4 years.Preoperative bilateral breast mammogram,breast dedicated MRI depictions and reports as well as histopathological reports were collected.Results Sensitivity of MRI outstood mammogram in each subgroups:84.7% vs.42.4% in DCIS (x2 =27.028,P =0.000),94.0% vs.80.0% in DCIS-MI group (x2 =4.540,P =0.040).And further analysis showed that MRI was more sensitive to high nuclear grade DCIS and DCIS-MI lesions than low nuclear grade ones (OR =3.471,P =0.031).Results of logistic regression analysis proved microcalcification was an independent predictive factor of mammogram sensitivity (OR =1 1.287,P =0.001).Conclusions Sensitivity of breast dedicated MRI is superior to mammogram in detecting DCIS and DCIS-MI groups.Lesions with microcalcifiation is an independent predictive marker which meant that mammogram would achieve high detection rate in cancers presented calcification on mammogram image when compared with non-calcification.Diagnostic performance of breast MRI is less affected by clinical and pathological characteristics of the early stage breast cancer patients but further increased detection rate is observed in DCIS and DCIS-MI with high nuclear grade lesions which indicated that MRI could detect more early stage cancers with relative more aggression biological behaviour and provide these patients with early surgical interventions before

  16. In search of a stem cell hierarchy in the human breast and its relevance to breast cancer evolution

    DEFF Research Database (Denmark)

    Villadsen, René

    2005-01-01

    homeostasis during mammary development, pregnancy, lactation and involution is brought about by the action of somatic stem cells characterized by longevity and multipotency. The progenies hereof eventually differentiate into structurally and functionally well-defined ductal-lobular units. During the past two...... of the concept of tumors as caricatures of tissue renewal. Thus, recent molecular classification of breast cancer based on genome wide expression analysis operates with different subtypes with specific reference to the normal luminal epithelial and myoepithelial/basal lineages in the breast. Apparently some...... tumors are lineage restricted and others differentiate more broadly as if they have preserved some stem-like properties. This holds promise for the existence of a stem cell hierarchy, the understanding of which may prove to be instrumental in further dissecting the histogenesis of breast cancer evolution...

  17. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  18. Microbial dysbiosis is associated with human breast cancer.

    Directory of Open Access Journals (Sweden)

    Caiyun Xuan

    Full Text Available Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications.

  19. Expression and significance of E-cadherin and Ki-67 in non-special type of invasive ductal carcinoma of breast%E-钙黏蛋白和Ki-67在非特殊型乳腺浸润性导管癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李玉红; 贾爱华; 鲁庆阳; 任玉波

    2011-01-01

    Objective To investigate the role of E-cadherin and antigen identified by monoclonal antibody Ki-67 in the occurrence and development of non-special type of invasive ductal carcinoma of breast. Methods The expression of E-cadherin and Ki-67 in 100 non-special type of invasive ductal carcinoma ( breast cancer group) and 20 breast fibroadenoma tissues ( fibroadenoma group) were detected by immunohistochemistry, and the relationship between these two antibodies and the clinicopathological features of non-special type of invasive ductal carcinoma were analyzed. Results The breast cancer group (67%) was lower than than the fibroadenoma group ( 100% ) in E-csdherin positive expression rate, and was ( 59% ) higher than the fibroadenoma group( 25% ) in Ki-67 positive expression rate, both P < 0.05; the expression of E-cadherin and Ki-67 were closely related to non-special type of invasive ductal carcinoma of breast in it's lymph node metastasis, TNM stage and histological grade, but not in patients' age and tumor diameter. Conclusions Reduced expression of E-cadherin and elevated expression of Ki-67 were closely related to non-special type of invasive ductal carcinoma of breast in it's occurrence and development, and detection of these two antibodies is helpful for determining the degree of malignancy and prognosis of non-special type of invasive ductal carcinoma of breast.%目的 探讨E-钙黏蛋白和增殖指数抗原Ki-67在非特殊型乳腺浸润性导管癌发生、发展中的作用.方法 采用免疫组化法检测E-钙黏蛋白和Ki-67在100份非特殊型乳腺浸润性导管癌组织(乳腺癌组)及20份乳腺纤维腺瘤组织(纤维腺瘤组)中的表达,并分析两者与非特殊型乳腺浸润性导管癌临床病理特征的关系.结果 乳腺癌组E-钙黏蛋白的阳性率(67%)明显低于纤维腺瘤组(100%),Ki-67的阳性率(59%)高于纤维腺瘤组(25%),P均<0.05;E-钙黏蛋白和Ki-67表达与非特殊型乳腺浸润性导管癌

  20. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Ankita Singh Rathore

    2014-01-01

    Full Text Available Background & objectives: Tumour infiltrating lymphocytes (TILs represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++ CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001 showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001 and CD8+ (OR=2.58, 95% CI=1.55-5.86, p0 =0.001 the least when compared to respective low (+ counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, p0 <0.001 showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, p0 <0.001 and CD3+ (OR=2.45, 95% CI=1.53-6.73, p0 =0.002 the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

  1. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  2. Ductal in situ carcinoma: is it ethical to consider the breast conserving?; Carcinome canalaire in situ: est-il ethique de considerer le traitement conservateur comme un standard?

    Energy Technology Data Exchange (ETDEWEB)

    Barillot, I. [Centre de Lutte Contre le Cancer Georges-Francois-Leclerc, Dept. de Radiotherapie, 21 - Dijon (France); Cutuli, B. [Polyclinique de Courlancy, Service de Radiotherapie-Cancerologie, 51 - Reims (France); Arnould, L. [Centre de Lutte Contre le Cancer Georges-Francois-Leclerc, Service d' Anatomie Pathologique, 21 - Dijon (France)

    2004-02-01

    The increasing incidence of DCIS during the past 20 years needs a continuous evaluation of the treatment strategies and a multidisciplinary decision process. The management of the DCIS remains a challenging issue in 2003. Mastectomy should still be considered as the reference treatment which is able to guarantee cure in almost all cases, whereas breast conserving surgery followed by radiation therapy is associated with 7-10% of local recurrence. However, the increasing knowledge of the predictive factors of the local recurrence allows to propose a conservative treatment strategy to a large amount of patients, without negative impact on their prognosis. This review presents the arguments that permit to justify, the reasoned choice of the different therapeutic options according to the clinico-pathological situations. (author)

  3. Comparison of Color Doppler Ultrasound and X-ray Mammography Photography in the Diagnostic Value of Breast Invasive Ductal Carcinoma%彩色多普勒超声对比钼靶X线摄影诊断乳腺浸润性导管癌的价值评价

    Institute of Scientific and Technical Information of China (English)

    张苗苗

    2016-01-01

    Objective To analyze the diagnosis value of color Doppler ultrasound in breast invasive ductal carcinoma.MethodsAnalysis of 50 cases of breast invasive ductal carcinoma with color Doppler ultrasound diagnosis and X-ray mammography photography,the diagnostic accuracy,the rate of misdiagnosis and missed diagnosis rate in the two methods were compared.Results The accuracy of ultrasound group was significantly higher than X-ray mammography,while the misdiagnosis rate was significantly lower,the difference was statisticaly significant(P<0.05).Conclusion Color Doppler ultrasound and X-ray mammography can effectively diagnose breast invasive ductal carcinoma. Ultrasound diagnosis can greatly improve the accuracy and reduce the rate of misdiagnosis and missed diagnosis rate.%目的:分析乳腺浸润性导管癌使用彩色多普勒超声进行诊断的价值。方法观察分析50例乳腺浸润性导管癌患者的彩色多普勒超声诊断结果和钼靶X线影摄的诊断结果,对比两组方法的诊断准确率、漏误诊率。结果超声组的准确率比钼靶组高,其漏诊率较低,组间差异具有统计学意义(P<0.05)。结论彩色多普勒超声和钼靶X线都能够有效诊断乳腺浸润性导管癌,超声诊断大大提高了准确率,降低了漏诊率。

  4. Prevention of the Angiogenic Switch in Human Breast Cancer

    Science.gov (United States)

    2009-03-01

    chronic myeloid leukaemia | colorectal cancer | Down syndrome | infantile haemangiomas | multiple myeloma | non-small-cell lung cancer | rheumatoid...Human Breast Cancer PRINCIPAL INVESTIGATOR: Donald Ingber, M.D., Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital...From - To) 15 FEB 2004 - 14 FEB 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prevention of the Angiogenic Switch in Human Breast Cancer 5b

  5. 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}.

  6. Exploring human breast milk composition by NMR-based metabolomics.

    Science.gov (United States)

    Praticò, Giulia; Capuani, Giorgio; Tomassini, Alberta; Baldassarre, Maria Elisabetta; Delfini, Maurizio; Miccheli, Alfredo

    2014-01-01

    Breast milk is a complex fluid evolutionarily adapted to satisfy the nutritional requirements of growing infants. In addition, milk biochemical and immunological components protect newborns against infective agents in the new environment. Human milk oligosaccharides, the third most abundant component of breast milk, are believed to modulate the microbiota composition, thus influencing a wide range of physiological processes of the infant. Human milk also contains a number of other bioactive compounds, the functional role of which has not yet been clearly elucidated. In this scenario, NMR-based metabolic profiling can provide a rapid characterisation of breast milk composition, thus allowing a better understanding of its nutritional properties.

  7. T Cell Coinhibition and Immunotherapy in Human Breast Cancer

    OpenAIRE

    Janakiram, Murali; Abadi, Yael M.; Sparano, Joseph A.; Zang, Xingxing

    2012-01-01

    Costimulation and coinhibition generated by the B7 family and their receptor CD28 family have key roles in regulating T lymphocyte activation and tolerance. These pathways are very attractive therapeutic targets for human cancers including breast cancer. Gene polymorphisms of B7x (B7-H4/B7S1), PD-1 (CD279), and CTLA-4 (CD152) are associated with increased risk of developing breast cancer although the underlying mechanisms are unclear. In human breast cancer microenvironment, up-regulation of ...

  8. Pattern of hormone receptors and human epidermal growth factor receptor 2 status in sub-Saharan breast cancer cases: Private practice experience.

    Science.gov (United States)

    Nwafor, C C; Keshinro, S O

    2015-01-01

    Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or negative (-). The IHC classification correlates well with intrinsic gene expression microarray categorization. ER-positive tumors may benefit from being treated with selective ER modulators and aromatase inhibitors, whereas patients with HER2/neu positive tumors have been shown to experience a significant survival advantage when treated with humanized monoclonal antibodies against HER2/neu. To determine ER/PR, HER2/neu expression and their association with histological prognostic markers in female breast carcinomas seen in a private diagnostic laboratory based in Lagos. Immunohistochemistry reports of breast cancer patients, which were diagnosed by histopathology section of a private diagnostic laboratory based in Lagos, Nigeria from August 2009 to August 2014. About 18.7% of breast cancers had IHC (ER, PR and HER2) done on them and were all females. The mean age of all subjects was 49.5 years (standard deviation, 13.2; range, 29-78 years). Most (95.8%) of the breast cancers were of invasive ductal carcinoma type, with 77.4% of them been >5 cm. IHC pattern was as follows: ER/PR+, HER2-=19 (39.6%), ER/PR-, HER2- (triple negative [TN])=14 (29.2%), ER/PR+, HER2+=9 (18.8%), ER/PR-, HER2+=6 (12.5%), corresponding to Lumina A, TN/basal-like, Lumina B and HER2 over expressed respectively. Triple negative breast cancers are common in our environment and affect young females most and could be contributory to the poorer prognosis of breast cancer in our environment.

  9. Carcinoma ductal in situ da mama: critérios para diagnóstico e abordagem em hospitais públicos de Belo Horizonte Approach of ductal carcinoma in situ of the breast in three public hospitals in Belo Horizonte

    Directory of Open Access Journals (Sweden)

    Marcio de Almeida Salles

    2006-12-01

    anatomo-pathological aspects in a series of patients with breast ductal carcinoma in situ (DCIS, attended in three public hospitals in Belo Horizonte (MG. METHODS: 179 cases of DCIS, that were selected from all the patients who had been diagnosed with breast cancer between 1985 and 2000, were studied retrospectively. After reviewing all the tissue sections, it was possible to collect all the clinical data, mammogram and treatment information of 85 cases. RESULTS: most patients were not symptomatic and the diagnosis had been done by mammogram (68.2%, being the microcalcification the most common radiological alteration. There has been a progressive increase in the diagnosis of DCIS along the years, following the introduction of periodical mammographic screening. The initial histopathological diagnosis and the review agreed in 72.9% of cases. In three cases, the original diagnosis of DCIS was not confirmed, being classified as atypical hyperplasia. Mammogram microcalcifications were confirmed in the pathological analysis in 95.6% of cases. Half of the patients was treated with mastectomy. All lymph nodes from axillary dissection were negative for metastases. CONCLUSIONS: The present study is in agreement with the recent literature, which shows an increase in the diagnosis of DCIS since 1990. There has been a great interobserver variation since the initial pathological diagnosis, which tended to malignancy and the present review. There were a great number of radical treatments, such as mastectomy and axillary dissection, which would probably be replaced by conservative treatment and sentinel lymph node biopsy nowadays, according to recent knowledge.

  10. Relation between radiographic BI-RADS scores and triple negativity in patients with ductal carcinomas

    OpenAIRE

    OKTAY, Murat; Oktay, Nilay Aydın; Besir, Fahri Halit; Buyukkaya, Ramazan; Erdem, Havva; Binnur ÖNAL; Ozaydın, İsmet; Yazıcı, Burhan

    2014-01-01

    The aim of this study was to investigate association of radiographic (BI-RADS 4 and 5) results and prognostic factors of invasive ductal carcinomas with their histopathological subtypes. A total of 103 patients histopathologically diagnosed with invasive ductal carcinoma of breast with in last five years period were enrolled. Of them, 69 patients who had radiological reports in were included from registry of Radiology Department; Duzce University Training and Research Hospital archives. BI-RA...

  11. Relation between radiographic BI-RADS scores and triple negativity in patients with ductal carcinomas

    OpenAIRE

    OKTAY, Murat; Oktay, Nilay Aydın; Besir, Fahri Halit; Buyukkaya, Ramazan; Erdem, Havva; ÖNAL, Binnur; Ozaydın, İsmet; Yazıcı, Burhan

    2014-01-01

    The aim of this study was to investigate association of radiographic (BI-RADS 4 and 5) results and prognostic factors of invasive ductal carcinomas with their histopathological subtypes. A total of 103 patients histopathologically diagnosed with invasive ductal carcinoma of breast with in last five years period were enrolled. Of them, 69 patients who had radiological reports in were included from registry of Radiology Department; Duzce University Training and Research Hospital archives. BI-RA...

  12. Treatment of low-risk ductal carcinoma in situ: is nothing better than something?

    Science.gov (United States)

    Benson, John R; Jatoi, Ismail; Toi, Masakazu

    2016-10-01

    The heterogeneous nature of ductal carcinoma in situ has been emphasised by data for breast-cancer screening that show substantial increases in the detection of early-stage non-invasive breast cancer but no noteworthy change in the incidence of invasive and distant metastatic disease. Indolent non-progressive forms of ductal carcinoma in situ are managed according to similar surgical strategies as high-risk disease, with extent of resection dictated by radiological and pathological estimates of tumour dimensions. Although adjuvant treatments might be withheld for low-risk lesions, surgical treatments incur potential morbidity, especially when mastectomy and breast reconstruction are done for widespread low-grade or intermediate-grade ductal carcinoma in situ. Low rates of deaths from breast cancer coupled with overdiagnosis within screening programmes have prompted a fundamental rethink of approaches to the management of both low-risk and high-risk ductal carcinoma in situ. Changes include active surveillance for low-risk lesions and a watchful waiting policy with intervention when invasive local recurrence after breast-conserving surgery is detected. Prediction of ipsilateral invasive recurrence is likely to be improved by integration of molecular biomarkers with conventional histopathological parameters. Moreover, further genetic interrogation of ductal carcinoma in situ might lead to a reclassification of some low-grade lesions as non-cancerous entities.

  13. Clinical impact of human breast milk metabolomics.

    Science.gov (United States)

    Cesare Marincola, Flaminia; Dessì, Angelica; Corbu, Sara; Reali, Alessandra; Fanos, Vassilios

    2015-12-01

    Metabolomics is a research field concerned with the analysis of metabolome, the complete set of metabolites in a given cell, tissue, or biological sample. Being able to provide a molecular snapshot of biological systems, metabolomics has emerged as a functional methodology in a wide range of research areas such as toxicology, pharmacology, food technology, nutrition, microbial biotechnology, systems biology, and plant biotechnology. In this review, we emphasize the applications of metabolomics in investigating the human breast milk (HBM) metabolome. HBM is the recommended source of nutrition for infants since it contains the optimal balance of nutrients for developing babies, and it provides a range of benefits for growth, immunity, and development. The molecular mechanisms beyond the inter- and intra-variability of HBM that make its composition unique are yet to be well-characterized. Although still in its infancy, the study of HBM metabolome has already proven itself to be of great value in providing insights into this biochemical variability in relation to mother phenotype, diet, disease, and lifestyle. The results of these investigations lay the foundation for further developments useful to identify normal and aberrant biochemical changes as well as to develop strategies to promote healthy infant feeding practices.

  14. In vitro methods to culture primary human breast epithelial cells.

    Science.gov (United States)

    Raouf, Afshin; Sun, Yu Jia

    2013-01-01

    Current evidence suggests that much like leukemia, breast tumors are maintained by a small subpopulation of tumor cells that have stem cell properties. These cancer stem cells are envisaged to be responsible for tumor formation and relapse. Therefore, knowledge about their nature will provide a platform to develop therapies to eliminate these breast cancer stem cells. This concept highlights the need to understand the mechanisms that regulate the normal functions of the breast stem cells and their immediate progeny as alterations to these same mechanisms can cause these primitive cells to act as cancer stem cells. The study of the primitive cell functions relies on the ability to isolate them from primary sources of breast tissue. This chapter describes processing of discarded tissue from reduction mammoplasty samples as sources of normal primary human breast epithelial cells and describes cell culture systems to grow single-cell suspensions prepared from these reduction samples in vitro.

  15. Infrared absorption of human breast tissues in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chenglin [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Physics Department of Yancheng Teachers' College, Yancheng 224002 (China); Zhang Yuan [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Yan Xiaohui [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China); Zhang Xinyi [Department of Physics, Surface Physics Laboratory (National Key laboratory), Synchrotron Radiation Research Center, Fudan University, Shanghai 200433 (China) and Shanghai Research Center of Acupuncture and Meridian, Pudong, Shanghai 201203 (China)]. E-mail: xy-zhang@fudan.edu.cn; Li Chengxiang [National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei 230029 (China); Yang Wentao [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China); Shi Daren [Cancer Hospital, Medical Center, Fudan University, Shanghai 200032 (China)

    2006-07-15

    The spectral characteristics of human breast tissues in normal status and during different cancerous stages have been investigated by synchrotron radiation based Fourier transform infrared (SR-FTIR) absorption spectroscopy. Thanks to the excellent synchrotron radiation infrared (IR) source, higher resolving power is achieved in SR-FTIR absorption spectra than in conventional IR absorption measurements. Obvious variations in IR absorption spectrum of breast tissues were found as they change from healthy to diseased, or say in progression to cancer. On the other hand, some specific absorption peaks were found in breast cancer tissues by SR-FTIR spectroscopic methods. These spectral characteristics of breast tissue may help us in early diagnosis of breast cancer.

  16. Ductal carcinoma in situ - update on risk assessment and management.

    Science.gov (United States)

    Pang, Jia-Min B; Gorringe, Kylie L; Fox, Stephen B

    2016-01-01

    Ductal carcinoma in situ (DCIS) accounts for ~20-25% of breast cancers. While DCIS is not life-threatening, it may progress to invasive carcinoma over time, and treatment intended to prevent invasive progression may itself cause significant morbidity. Accurate risk assessment is therefore necessary to avoid over- or undertreatment of an individual patient. In this review we will outline the evidence for current management of DCIS, discuss approaches to DCIS risk assessment and challenges facing identification of novel DCIS biomarkers.

  17. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  18. Up-regulation of human arrest-defective 1 protein is correlated with metastatic phenotype and poor prognosis in breast cancer.

    Science.gov (United States)

    Wang, Ze-Hua; Gong, Jun-Li; Yu, M; Yang, H; Lai, J H; Ma, M X; Wu, H; Li, L; Tan, D Y

    2011-01-01

    Human arrest defective 1 protein (ARD1), as a N-terminal acetyltransferase, has been reported to play a crucial role in tumorigenesis, but the results are somewhat controversial. To explore the clinical and pathological significance of ARD1 in breast tumorigenesis, we analyzed ARD1 status in multiple types of breast disease. The expression of ARD1 protein was assessed by immunohistochemistry in 356 cases including 82 invasive ductal carcinomas (IDC), 159 fibroadenomas, 66 hyperplasia of mammary glands, 19 inflammatory breast disease, 30 breast cysts, and in 29 postoperative treatment patients. We assessed the relationship of ARD1 protein with clinical and pathological characteristics using χ2 test. ARD1 protein was observed at 61.0% (50/82), 54.7% (87/159), 37.9% (25/66), 36.8% (7/19) in IDC, fibroadenoma, hyperplasia, and inflammation, respectively, and less than 30.0% for breast cyst. Thus, high ARD1 expression correlated with breast cancer (relative risk = 1.32, P < 0.005). Moreover, the level of ARD1 protein in carcinoma patients was distinctly related to lymph node metastasis and ER status, with 94.0% (47/50) as copmpared to 6.0% (3/50) in metastatic and non-metastatic (P < 0.001), and 84.0% (42/50) and 16.0% (8/50) for ER + and ER - (P < 0.01), respectively. In addition, the level of ARD1 appeared to have potential for evaluation of prognosis in breast cancer patients after postoperative therapy. These results suggest that ARD1 expression may be as a potential target for exploring the mechanism of breast cancer metastasic to lymph nodes and hormone-responsive regulation.

  19. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  20. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Science.gov (United States)

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  1. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  2. Comprehensive molecular portraits of human breast tumours.

    Science.gov (United States)

    2012-10-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

  3. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data.

    Science.gov (United States)

    Kiarashi, Nooshin; Nolte, Adam C; Sturgeon, Gregory M; Segars, William P; Ghate, Sujata V; Nolte, Loren W; Samei, Ehsan; Lo, Joseph Y

    2015-07-01

    Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power-law descriptions of the phantom images

  4. Development of realistic physical breast phantoms matched to virtual breast phantoms based on human subject data

    Energy Technology Data Exchange (ETDEWEB)

    Kiarashi, Nooshin [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Nolte, Adam C. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Sturgeon, Gregory M.; Ghate, Sujata V. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, William P. [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Nolte, Loren W. [Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Samei, Ehsan [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Electrical and Computer Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27708 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States); and others

    2015-07-15

    Purpose: Physical phantoms are essential for the development, optimization, and evaluation of x-ray breast imaging systems. Recognizing the major effect of anatomy on image quality and clinical performance, such phantoms should ideally reflect the three-dimensional structure of the human breast. Currently, there is no commercially available three-dimensional physical breast phantom that is anthropomorphic. The authors present the development of a new suite of physical breast phantoms based on human data. Methods: The phantoms were designed to match the extended cardiac-torso virtual breast phantoms that were based on dedicated breast computed tomography images of human subjects. The phantoms were fabricated by high-resolution multimaterial additive manufacturing (3D printing) technology. The glandular equivalency of the photopolymer materials was measured relative to breast tissue-equivalent plastic materials. Based on the current state-of-the-art in the technology and available materials, two variations were fabricated. The first was a dual-material phantom, the Doublet. Fibroglandular tissue and skin were represented by the most radiographically dense material available; adipose tissue was represented by the least radiographically dense material. The second variation, the Singlet, was fabricated with a single material to represent fibroglandular tissue and skin. It was subsequently filled with adipose-equivalent materials including oil, beeswax, and permanent urethane-based polymer. Simulated microcalcification clusters were further included in the phantoms via crushed eggshells. The phantoms were imaged and characterized visually and quantitatively. Results: The mammographic projections and tomosynthesis reconstructed images of the fabricated phantoms yielded realistic breast background. The mammograms of the phantoms demonstrated close correlation with simulated mammographic projection images of the corresponding virtual phantoms. Furthermore, power

  5. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  6. Hydroxytyrosol protects against oxidative DNA damage in human breast cells.

    Science.gov (United States)

    Warleta, Fernando; Quesada, Cristina Sánchez; Campos, María; Allouche, Yosra; Beltrán, Gabriel; Gaforio, José J

    2011-10-01

    Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol's effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  7. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    Science.gov (United States)

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Clinicopathological significance of PTPN12 expression in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Xunyi [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China); Yuan, Zhentao [Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying Shandong Province (China); Jiang, Dandan; Li, Funian [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China)

    2012-10-15

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.

  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. Fine needle aspiration cytology diagnosis of ductal lesions of breast%应用细针吸取细胞技术诊断乳腺导管病变的细胞学指标

    Institute of Scientific and Technical Information of China (English)

    狄方; 王念黎

    2010-01-01

    Objective To find out the most effective and combined cytomorphologic criteria trying to set up an effective diagnostic model for breast ductal lesion in fine needle aspiration cytology (FNAC).Methods A total of 400 breast FNAC cases were collected with follow-up information of more than six years. A retrospective analysis including 104 non-proliferative breast diseases,163 proliferarive breast diseases and 133 carcinomas basing on the diagnostic results of surgical biopsies. Altogether,60 cytomorphologic variables were counted for the evaluation of each case,including 4 main categories: the cellularity and components,natures of background,cellular arrangements and the cellular features. According to the quantity or the classification stage,the variables were semi-quantitatively scored. Multiple step-wise logistic regression (SPSS)and classification tree model (SAS)were performed to determine the significant and combined variables predictive for the diagnosis of non-proliferative lesion,proliferative breast diseases and carcinoma,respectively. Results (1)Among 400 benign and malignant cases studied,and basing on the result of analyses of multiple step-wise logistic regression system,intermingling of myoepithelial cells within the epithelial cluster (P < 0. 05 ),presence of large epithelial cell cluster (P < 0. 05),presence of small epithelial cell cluster (P < 0. 05),cytoplasmic vacuoles (P < 0.05)and figures of "progressive intussusception" of cells (P <0. 1)were selected as the effectively differential diagnostic criteria for the benign and malignant lesions. However,according to the classification tree model,the most useful variable selected associating with the benign lesion was intermingling of myoepithelial cells within epithelial cluster. The diagnostic accuracy will be increased to 94. 4% ,if another criterion,presence of a big amount of large epithelial clusters,was used as the second useful variable in combination. Presence of a moderate to large amount

  11. Surfactant protein A expression in human normal and neoplastic breast epithelium.

    Science.gov (United States)

    Braidotti, P; Cigala, C; Graziani, D; Del Curto, B; Dessy, E; Coggi, G; Bosari, S; Pietra, G G

    2001-11-01

    We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples. Sections were immunostained with polyclonal anti-Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase-polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas. The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.

  12. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  13. The expressions of HER-2, p16 and p53 protein in infiltrating ductal breast carcinoma and its significance%HER-2、p16、p53蛋白在乳腺浸润性导管癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    胡爱侠; 孙淼淼; 陈奎生

    2012-01-01

    Purpose To investigate the expressions of HER-2, pl6 and p53 protein in breast infiltrating ductal carcinoma and its clinical significance. Methods f49 patients were confirmed as breast infiltrating ductal cancer and were selected in our study which hospitalized from July in 2008 to December in 20f 0. Then pathologic and clinical data of patients were collected and the expressions of HER-2, p16 and p53 protein in breast infiltrating ductal cancer and normal tissues was detected. Results The positive rate of HER-2, pf6 and p53 protein in breast infiltrating ductal cancer was 23. 5% , 3f. 5% and 5f. 0% , repectively. Over-expression of HER-2 had a significant correlation with axillary lymph node metastasis and histological grade ( χ2 =5. 687, χ2 = 5. 924, both P < 0. 05 ). There was significant difference in the positive expression of p16 between the different age groups ( χ2 =4. 213 , P <0. 05 ). And there was significant difference in the positive expression of p53 between different histological grading ( χ2 =6. 378,P < 0. 05 ). There was a significant correlation between the expressions of HER-2, pl6 and disease-free survival time after operation. There was significant correlation between pl6 and p53 ( r = 0. 282 , P < 0. 05 ). Conclusions The expressions of HER-2, pl6 , and p53 protein are closely related with the development of breast invasive ductal cancer and thus they could be used as an important indicator for guiding treatment and predicting prognosis.%目的 探讨HER-2、p16、p53蛋白在乳腺浸润性导管癌中的表达情况及其临床意义.方法 收集2008年7月~2010年12月商丘市中心医院行手术治疗,术后证实为乳腺浸润性导管癌患者149例,检测HER-2、p16、p53蛋白在乳腺浸润性导管癌中以及正常组织中的表达情况.结果 乳腺浸润性导管癌HER-2过表达,阳性率为23.5%;p16、p53阳性率分别为31.5%和51.0%;HER-2过表达与腋窝淋巴结转移、组织学分级存在明显相关性(χ2

  14. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  15. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

    Full Text Available MicroRNAs (miRNAs are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  16. CHL1 is involved in human breast tumorigenesis and progression

    Energy Technology Data Exchange (ETDEWEB)

    He, Li-Hong [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ma, Qin [Department of Oncology, The General Hospital of Tianjin Medical University, Tianjin (China); Shi, Ye-Hui [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie; Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Shu-Fen [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Tong, Zhong-Sheng, E-mail: 83352162@qq.com [Medical Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-08-23

    Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

  17. Mutagens in human breast lipid and milk: the search for environmental agents that initiate breast cancer.

    Science.gov (United States)

    Phillips, David H; Martin, Francis L; Williams, J Andrew; Wheat, Luise M C; Nolan, Lisa; Cole, Kathleen J; Grover, Philip L

    2002-01-01

    Epidemiological studies indicate the involvement of environmental factors in the etiology of breast cancer, but have not provided clear indications of the nature of the agents responsible. Several environmental carcinogens are known to induce mammary tumors in rodents, and the abundance of adipose tissue in the human breast suggests that the epithelial cells, from which breast tumors commonly arise, could be exposed to lipid-soluble carcinogens sequestered by the adipose tissue. In this report we review our studies in which we have examined human mammary lipid, obtained from elective reduction mammoplasties from healthy donors, and human milk from healthy mothers, for the presence of components with genotoxic activity in several in vitro assays. A significant proportion of lipid extracts induced mutations in bacteria and micronuclei in mammalian cells. They also caused DNA damage, detected as single-strand breaks in the alkaline single-cell gel electrophoresis (comet) assay, in both the MCL-5 cell line and in primary cultures of human mammary epithelial cells. Genotoxic activity was also found in a significant proportion of extracts of human breast milk. Viable cells recovered from milk samples showed evidence of DNA damage and were susceptible to comet formation by genotoxic agents in vitro. Genotoxic activity was found to be less prevalent in milk samples from countries of lower breast cancer incidence (the Far East) compared with that in samples from the UK. The agents responsible for the activity in milk appear to be moderately polar lipophilic compounds and of low molecular weight. Identification of these agents and their sources may hold clues to the origins of breast cancer.

  18. Axillary node dissection in ductal carcinoma in situ.

    Science.gov (United States)

    Parker, R G; Berkbigler, D; Rees, K; Leung, K M; Legorreta, A P

    1998-04-01

    Intraductal carcinoma of the breast has become a well-defined entity that has been more frequently diagnosed since the introduction of mammography. For many years, the usual treatment has been mastectomy, often with axillary lymph node dissection. Concurrent with documentation that breast conservation treatment has been effective for many invasive breast cancers, such treatment has been introduced for noninvasive breast cancers (ductal carcinoma in situ and lobular cancer in situ). However, there is no basis for axillary dissection because tumor cells are contained by the basement membrane and should not metastasize. In this study, 107 axillary dissections were carried out, with an average of 20 nodes identified, and a single metastasis was identified.

  19. The mRNA expression of SATB1 and SATB2 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mansel Robert

    2009-07-01

    increasing tumour grade (grade 1 vs. grade 3 p = 0.035. SATB2 was associated with ER positivity (ER(- vs. ER(+ p = 0.0283 within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433. Conclusion SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SATB1 acts as a 'master genome organizer' in human breast carcinogenesis.

  20. Comprehensive molecular portraits of human breast tumours

    NARCIS (Netherlands)

    Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.; Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Hoadley, Katherine A.; Auman, J. Todd; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Adams, Michael; Booker, Jessica; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Triche, Timothy; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Baylin, Stephen B.; Laird, Peter W.; Creighton, Chad J.; Donehower, Lawrence A.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Erkkila, Timo; Lin, Jake; Thorsson, Vesteinn; Zhang, Wei; Shmulevich, Ilya; Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Taylor, Barry S.; Ladanyi, Marc; Sander, Chris; Anur, Pavana; Spellman, Paul T.; Lu, Yiling; Liu, Wenbin; Verhaak, Roel R. G.; Mills, Gordon B.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Scott, Gary K.; Yau, Christina; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian; Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa; Tarvin, Katie; Saller, Charles; Sandusky, George; Mitchell, Colleen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Dolzhansky, Oleg; Abramov, Mikhail; Voronina, Olga; Potapova, Olga; Marks, Jeffrey R.; Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Duc Phu, Bui; Hajek, Richard; Phi Hung, Nguyen; Viet The Phuong, Tran; Quyet Thang, Huynh; Khan, Khurram Zaki; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.; King, Tari A.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stoeppler, Hubert; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley; Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam; Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen; Dhir, Rajiv; Bhargava, Rohit; Brufsky, Adam; Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh; Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Kovatich, Albert J.; Ellis, Matthew J.; King, Tari A.; Hu, Hai; Couch, Fergus J.; Mural, Richard J.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Ingle, James N.; Luo, Chunqing; Chen, Yaqin; Marks, Jeffrey R.; Waldman, Frederic; Wiznerowicz, Maciej; Bose, Ron; Chang, Li-Wei; Beck, Andrew H.; Gonzalez-Angulo, Ana Maria; Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David; Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Eley, Greg; Ferguson, Martin L.; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Buetow, Kenneth; Fielding, Peter; Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.

    2012-01-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression sub

  1. Comprehensive molecular portraits of human breast tumours

    NARCIS (Netherlands)

    Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.; Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Nguyen, Huy; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Hoadley, Katherine A.; Auman, J. Todd; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Adams, Michael; Booker, Jessica; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Triche, Timothy; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Baylin, Stephen B.; Laird, Peter W.; Creighton, Chad J.; Donehower, Lawrence A.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Erkkila, Timo; Lin, Jake; Thorsson, Vesteinn; Zhang, Wei; Shmulevich, Ilya; Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Taylor, Barry S.; Ladanyi, Marc; Sander, Chris; Anur, Pavana; Spellman, Paul T.; Lu, Yiling; Liu, Wenbin; Verhaak, Roel R. G.; Mills, Gordon B.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Scott, Gary K.; Yau, Christina; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Thusberg, Janita; Mooney, Sean; Ng, Sam; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian; Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa; Tarvin, Katie; Saller, Charles; Sandusky, George; Mitchell, Colleen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Dolzhansky, Oleg; Abramov, Mikhail; Voronina, Olga; Potapova, Olga; Marks, Jeffrey R.; Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej; Van Le, Xuan; Kohl, Bernard; Viet Tien, Nguyen; Thorp, Richard; Van Bang, Nguyen; Sussman, Howard; Duc Phu, Bui; Hajek, Richard; Phi Hung, Nguyen; Viet The Phuong, Tran; Quyet Thang, Huynh; Khan, Khurram Zaki; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.; King, Tari A.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto; Waldman, Frederic; Stoeppler, Hubert; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley; Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam; Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen; Dhir, Rajiv; Bhargava, Rohit; Brufsky, Adam; Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh; Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Kovatich, Albert J.; Ellis, Matthew J.; King, Tari A.; Hu, Hai; Couch, Fergus J.; Mural, Richard J.; Stricker, Thomas; White, Kevin; Olopade, Olufunmilayo; Ingle, James N.; Luo, Chunqing; Chen, Yaqin; Marks, Jeffrey R.; Waldman, Frederic; Wiznerowicz, Maciej; Bose, Ron; Chang, Li-Wei; Beck, Andrew H.; Gonzalez-Angulo, Ana Maria; Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David; Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Eley, Greg; Ferguson, Martin L.; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Buetow, Kenneth; Fielding, Peter; Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.

    2012-01-01

    We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression sub

  2. Status of Intraductal Therapy for Ductal Carcinoma in Situ

    Science.gov (United States)

    Flanagan, Meghan; Love, Susan

    2010-01-01

    The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS. PMID:21124756

  3. Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.

    Science.gov (United States)

    Cotarelo, Cristina L; Schad, Arno; Kirkpatrick, Charles James; Sleeman, Jonathan P; Springer, Erik; Schmidt, Marcus; Thaler, Sonja

    2016-11-15

    Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity.

  4. Human breast milk: A review on its composition and bioactivity.

    Science.gov (United States)

    Andreas, Nicholas J; Kampmann, Beate; Mehring Le-Doare, Kirsty

    2015-11-01

    Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant's needs. In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota. Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding. Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants.

  5. Ductal lavage and ductoscopy: the opportunities and the limitations.

    Science.gov (United States)

    Khan, Seema A; Baird, Carol; Staradub, Valerie L; Morrow, Monica

    2002-08-01

    Two related techniques of breast epithelial sampling have emerged in the past several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated at their orifices and lavaged with saline while the breast is intermittently massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices are dilated, intubated with a microendoscope, and the lumen directly visualized. Both of these techniques have significant potential in terms of allowing the repeated sampling of ductal epithelium over time and, as such, have generated considerable enthusiasm. However, data regarding the impact of these techniques on the detection of significant breast disease is very scant. It is important at the outset of the assessment of this new technology that breast cancer clinicians and clinical researchers think carefully about the standards of evidence that need to be met regarding the benefits of these procedures before they are widely adopted. In this review of the rationale and early results of these procedures, we attempt to define some of these evidentiary requirements.

  6. Vitamin D content in human breast milk

    DEFF Research Database (Denmark)

    Við Streym, Susanna; Højskov, Carsten S; Møller, Ulla Kristine

    2016-01-01

    BACKGROUND: Parents are advised to avoid the direct sun exposure of their newborns. Therefore, the vitamin D status of exclusively breastfed newborns is entirely dependent on the supply of vitamin D from breast milk. OBJECTIVES: We explored concentrations of ergocalciferol (vitamin D2......) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo......, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH)D...

  7. Detection of Volatile Metabolites of Garlic in Human Breast Milk.

    Science.gov (United States)

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-06-06

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO₂). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO₂ are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  8. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Laura Scheffler

    2016-06-01

    Full Text Available The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O, as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2. Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  9. Educational Counseling in Improving Communication and Quality of Life in Spouses and Breast Cancer Patients

    Science.gov (United States)

    2014-12-29

    Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Psychosocial Effects of Cancer and Its Treatment; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  10. Therapeutic monoclonal antibodies in human breast milk: a case study.

    Science.gov (United States)

    Ross, Elle; Robinson, Steven E; Amato, Carol; McMillan, Colette; Westcott, Jay; Wolf, Tiffany; Robinson, William A

    2014-04-01

    Recently, therapeutic monoclonal antibodies have been introduced for the treatment of advanced melanoma and other diseases. It remains unclear whether these drugs can be safely administered to women who are breast feeding because of the potential hazardous side effects for nursing infants. One such therapy for metastatic melanoma is ipilimumab, a human monoclonal antibody that blocks cytotoxic T-lymphocyte-antigen-4, and is the preferred treatment for patients with metastatic melanoma when other molecular therapies are not viable. This study measured ipilimumab levels in the breast milk of a patient undergoing treatment that were enough to raise concerns for a nursing infant exposed to ipilimumab.

  11. Monitoring the progression from intraductal carcinoma to invasive ductal carcinoma based on multiphoton microscopy

    Science.gov (United States)

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

    2015-09-01

    Intraductal carcinoma is a precancerous lesion of the breast and the immediate precursor of invasive ductal carcinoma. Multiphoton microscopy (MPM) was used to monitor the progression from intraductal carcinoma to invasive ductal carcinoma, which can improve early detection of precursor lesions and halt progression to invasive neoplastic disease. It was found that MPM has the capability to reveal the qualitative changes in features of cells, structure of basement membranes, and architecture of collagens during the development from intraductal carcinoma to invasive ductal carcinoma, as well as the quantitative alterations in nuclear area, circle length of basement membrane, and collagen density. Combined with intra-fiberoptic ductoscopy or transdermal biopsy needle, MPM has the potential to provide immediate histological diagnosis of tumor progression in the field of breast carcinoma.

  12. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland

    Directory of Open Access Journals (Sweden)

    Laura McDonald

    2014-05-01

    Full Text Available RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER/progesterone receptor (PR/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.

  13. RUNX2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of Runx2 perturbs differentiation in the mouse mammary gland.

    Science.gov (United States)

    McDonald, Laura; Ferrari, Nicola; Terry, Anne; Bell, Margaret; Mohammed, Zahra M; Orange, Clare; Jenkins, Alma; Muller, William J; Gusterson, Barry A; Neil, James C; Edwards, Joanne; Morris, Joanna S; Cameron, Ewan R; Blyth, Karen

    2014-05-01

    RUNX2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. Upregulation of RUNX2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. However, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. Using a human tumour tissue microarray, we show that high RUNX2 expression is significantly associated with oestrogen receptor (ER)/progesterone receptor (PR)/HER2-negative breast cancers and that patients with high RUNX2 expression have a poorer survival rate than those with negative or low expression. We confirm RUNX2 as a gene that has a potentially important functional role in triple-negative breast cancer. To investigate the role of this gene in breast cancer, we made a transgenic model in which Runx2 is specifically expressed in murine mammary epithelium under the control of the mouse mammary tumour virus (MMTV) promoter. We show that ectopic Runx2 perturbs normal development in pubertal and lactating animals, delaying ductal elongation and inhibiting lobular alveolar differentiation. We also show that the Runx2 transgene elicits age-related, pre-neoplastic changes in the mammary epithelium of older transgenic animals, suggesting that elevated RUNX2 expression renders such tissue more susceptible to oncogenic changes and providing further evidence that this gene might have an important, context-dependent role in breast cancer.

  14. Spatial and temporal age-related spectral alterations in benign human breast tissue

    Science.gov (United States)

    Theophilou, Georgios; Fogarty, Simon W.; Trevisan, Júlio; Strong, Rebecca J.; Heys, Kelly A.; Patel, Imran I.; Stringfellow, Helen F.; Martin-Hirsch, Pierre L.; Martin, Francis L.

    2016-02-01

    Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.

  15. Breast magnetic resonance imaging in patients with occult breast carcinoma: evaluation on feasibility and correlation with histopathological findings

    Institute of Scientific and Technical Information of China (English)

    LU Hong; XU Yi-lin; ZHANG Shu-ping; LANG Rong-gang; Chi S.Zee; LIU Pei-fang; FU Li

    2011-01-01

    Background As an uncommon presentation, occult primary breast cancer remains a diagnostic and therapeutic challenge in clinical practice. This study aimed to retrospectively assess the feasibility of breast magnetic resonance imaging (MRI) in patients with malignant axillary lymphadenopathy and unknown primary malignancy, and correlation with histopathological characteristics.Methods A total of 35 women with occult breast carcinoma were evaluated with dynamic contrast-enhanced breast MRI. Whole seriate section was used in all cases. MRI performance was assessed and correlated with histopathological findings.Results Twenty-one of 35 patients were found to have primary breast carcinoma histologically. Twenty of the 21 patients had abnormal MR findings and 1 patient had a normal MRI study. Of the remaining 14 patients, 10 were negative on both MRI and surgery. Four had suspicious enhancement on MRI and no corresponding tumor was found. Lesions with mass enhancement were found in 55% (11/20) and ductual and segmental enhancement in 45%. The average diameter of the primary tumors was 15 mm. Invasive ductal carcinomas were found in 81% (17/21). One of 17 invasive ductual carcinomas was too small to be graded. Fourteen of the remaining 16 were classified as grade II and 2 as grade I. Thirty-two of the 35 patients had received estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 examinations and the 12 of 32 were triple-negative breast carcinoma.Conclusions Mass lesions with small size and lesions with ductal or segment enhancement are common MRI features in patients with occult breast cancer. The dominant types of primary tumors are invasive ductal carcinoma with moderate histopathological grade. The rate of triple-negative breast carcinoma may be higher in occult breast cancer.

  16. Infiltrating Ductal Carcinoma Arising in Fibroadenoma and Associated Proliferative Mammary Disease in a 38 Years Old Female -A Rare Case Report

    OpenAIRE

    Kamra, Hemlata T; Swaran Kaur; Mukesh Sangwan; Ruchi Agarwal; Sanjay Verma

    2017-01-01

    Infiltrating ductal carcinoma arising in a fibroadenoma is a rare incidental finding. Incidence is 0.002-0.0125%. Women having proliferative disease without atypia have a twofold elevation in their risk for subsequent invasive breast cancer. We here present a case report in a 38 years female having fibroadenoma, intraductal papilloma and fibocystic disease of breast who subsequently developed invasive ductal carcinoma in the fibroadenoma. Thus these lesions can be considered to have increased...

  17. Infiltrating Ductal Carcinoma Arising in Fibroadenoma and Associated Proliferative Mammary Disease in a 38 Years Old Female -A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Hemlata T. Kamra

    2017-01-01

    Full Text Available Infiltrating ductal carcinoma arising in a fibroadenoma is a rare incidental finding. Incidence is 0.002-0.0125%. Women having proliferative disease without atypia have a twofold elevation in their risk for subsequent invasive breast cancer. We here present a case report in a 38 years female having fibroadenoma, intraductal papilloma and fibocystic disease of breast who subsequently developed invasive ductal carcinoma in the fibroadenoma. Thus these lesions can be considered to have increased risk of developing malignancy.

  18. 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 ...

  19. KiSS-1 expression in human breast cancer.

    Science.gov (United States)

    Martin, Tracey A; Watkins, Gareth; Jiang, Wen G

    2005-01-01

    The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3,124+/-1,262 vs 2,397+/-1,181) and significantly increased in node positive tumours compared to node negative (3,637+/-1,719 vs 2,653+/-1,994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4,631+/-3,024 vs 2,280+/-1,403) whereas expression of the receptor was reduced (480+/-162 vs 195+/-134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.

  20. β-Arrestin2 regulates lysophosphatidic acid-induced human breast tumor cell migration and invasion via Rap1 and IQGAP1.

    Directory of Open Access Journals (Sweden)

    Mistre Alemayehu

    Full Text Available β-Arrestins play critical roles in chemotaxis and cytoskeletal reorganization downstream of several receptor types, including G protein-coupled receptors (GPCRs, which are targets for greater than 50% of all pharmaceuticals. Among them, receptors for lysophosphatidic acid (LPA, namely LPA(1 are overexpressed in breast cancer and promote metastatic spread. We have recently reported that β-arrestin2 regulates LPA(1-mediated breast cancer cell migration and invasion, although the underlying molecular mechanisms are not clearly understood. We show here that LPA induces activity of the small G protein, Rap1 in breast cancer cells in a β-arrestin2-dependent manner, but fails to activate Rap1 in non-malignant mammary epithelial cells. We found that Rap1A mRNA levels are higher in human breast tumors compared to healthy patient samples and Rap1A is robustly expressed in human ductal carcinoma in situ and invasive tumors, in contrast to the normal mammary ducts. Rap1A protein expression is also higher in aggressive breast cancer cells (MDA-MB-231 and Hs578t relative to the weakly invasive MCF-7 cells or non-malignant MCF10A mammary cells. Depletion of Rap1A expression significantly impaired LPA-stimulated migration of breast cancer cells and invasiveness in three-dimensional Matrigel cultures. Furthermore, we found that β-arrestin2 associates with the actin binding protein IQGAP1 in breast cancer cells, and is necessary for the recruitment of IQGAP1 to the leading edge of migratory cells. Depletion of IQGAP1 blocked LPA-stimulated breast cancer cell invasion. Finally, we have identified that LPA enhances the binding of endogenous Rap1A to β-arrestin2, and also stimulates Rap1A and IQGAP1 to associate with LPA(1. Thus our data establish novel roles for Rap1A and IQGAP1 as critical regulators of LPA-induced breast cancer cell migration and invasion.

  1. 自动乳腺全容积成像在乳腺导管原位癌诊断中的应用价值%The diagnostic value of the automated breast volume scanner in ductal carcinomain situ

    Institute of Scientific and Technical Information of China (English)

    包凌云; 谭艳娟; 朱罗茜; 许晓静; 孔凡雷; 刘坚; 朱庆庆

    2015-01-01

    ObjectiveTo investigate the value of the automated breast volume scanner (ABVS) in the diagnosis of ductal carcinomain situ(DCIS).MethodsSixty-seven patients who were diagnosed as DCIS by histopathology from December, 2010 to December, 2012 were retrospectively analyzed. Their image results and detection rates of mammography, conventional ultrasound and ABVS were analyzed and compared by Nonparametric Cochran'sQ test, and the further comparison were performed between groups by McNemar test.ResultsThe cases diagnosed as mass (with or without microcalcifications) by mammography, conventional ultrasound and ABVS were 13 (19%), 22 (33%) and 25 (37%), respectively. The detection rates of conventional ultrasound and ABVS were higher than mammography, and the differences were statistically significant (χ2=7.11, 10.08, bothP0.05). The cases diagnosed as simple microcalcification or associated with microcalcification by mammography, conventional ultrasound and ABVS were 42 (63%), 30 (45%) and 39 (58%), respectively. The detection rates of simple microcalcification or associated with microcalcifications by mammography and ABVS were higher than conventional ultrasound, and the differences were statistically significant (χ2=8.64, 5.82, bothP0.05). The detection rates of DCIS by mammography, conventional ultrasound and ABVS were 84%, 70% and 91%. The detection rates of DCIS by mammography and ABVS were higher than conventional ultrasound, and the differences were statistically significant. But the rate between mammography and ABVS showed no statistical significance.ConclusionsABVS can improve the ultronic detection rate of breast DCIS. Its detection rate is similar with mammography performance.%目的探讨自动乳腺全容积成像(ABVS)在乳腺导管原位癌(DCIS)诊断中的应用价值。方法回顾性分析2010年12月至2012年12月杭州市第一人民医院收治的经手术病理证实的67例乳腺DCIS患者的钼靶X线、常规超声及ABVS表现。

  2. Mammary ductoscopy and ductal washings for the evaluation of patients with pathologic nipple discharge.

    Science.gov (United States)

    Vaughan, Aislinn; Crowe, Joseph P; Brainard, Jennifer; Dawson, Andrea; Kim, Julian; Dietz, Jill R

    2009-01-01

    The majority of breast diseases result from lesions of the ductal epithelium. Mammary ductoscopy allows for visualization of intraductal abnormalities, and ductoscopic lavage provides thousands of cells for analysis. We reviewed our experience of 89 cases of patients with pathologic nipple discharge (PND) undergoing ductoscopy-directed duct excision and collection of ductal washings. Patients undergoing ductoscopy-directed duct excision with ductal washings had an 88% abnormal pathology rate. Most abnormalities were benign (71% papillomas), but the atypia rate for this group was 62%. The combination of visualization and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. Cellular yields for this technique were excellent with most specimens yielding >5,000 epithelial cells per high powered field and with evaluable ductal cells in 82% of specimens. Mammary ductoscopy offers the advantage of a high lesion localization rates with intraoperative guidance. The most accurate tool was the combination of ductal washings and ductoscopic visualization, but preoperative use of these techniques is not helpful in most cases. Greater than 90% of patients with PND are found to have a lesion on pathologic examination when using this technique for directed duct excision. Of interest, ductal washings obtained from symptomatic patients with benign diseases are often atypical.

  3. Use of magnetic resonance imaging for detecting clinically and mammographically occult ductal carcinoma in situ.

    Science.gov (United States)

    Lo, G; Cheung, Polly S Y

    2008-06-01

    We report on two cases where breast magnetic resonance imaging examination changed clinical management. Breast magnetic resonance imaging is now recognised as an indispensable adjunctive examination to mammography and ultrasound. In each of the two cases described, breast magnetic resonance imaging revealed unsuspected, extensive, and mammographically and ultrasonologically occult, ductal carcinoma in situ. In each of these cases, planned breast conserving surgery was changed to mastectomy. The success of breast conservation treatment depends on removal of all tumour with clear margins at the time of surgery. Magnetic resonance imaging is now considered the most sensitive method for evaluating the extent of breast cancer. Breast magnetic resonance imaging has a very high sensitivity for invasive carcinoma (near 100%), and recent studies show its specificity in high-risk patients is between 93 and 99%. Magnetic resonance imaging may well be proven an important adjunctive examination in patients who have dense breasts or extensive fibrocystic change.

  4. Human breast milk and the gastrointestinal innate immune system.

    Science.gov (United States)

    Jakaitis, Brett M; Denning, Patricia W

    2014-06-01

    The gastrointestinal (GI) tract is a large potential portal for multiple infectious agents to enter the human body. The GI system performs multiple functions as part of the neonate's innate immune system, providing critical defense during a vulnerable period. Multiple mechanisms and actions are enhanced by the presence of human breast milk. Bioactive factors found in human milk work together to create and maintain an optimal and healthy environment, allowing the intestines to deliver ideal nutrition to the host and afford protection by a variety of mechanisms.

  5. Human exposure to endocrine disruptors and breast milk.

    Science.gov (United States)

    Stefanidou, M; Maravelias, C; Spiliopoulou, C

    2009-09-01

    Endocrine system is one of the most sensitive communication networks of the human body which influences all aspects of human health and well-being, including reproductive potential, cognitive functions, thyroid and metabolism, digestion and hormonal balance. In recent years basic laboratory research has been focused on the potential relationship between environmental contaminants and cellular endocrine function. Environmental contaminants are ubiquitous in the environment, alter endocrine physiology and produce endocrine disruption without acting as classic toxicants. These endocrine disruptors (EDCs) are lipophilic and stored for long periods of time in the adipose tissue. Maternal exposure to EDCs during pregnancy and lactation has as a result the exposure of the fetus and neonate through placenta and breast milk. It has been recognized that human milk is the best natural food for neonates providing immunologic, developmental and practical advantages throughout childhood. However, contamination of human milk by the presence of environmental toxicants is widespread through the past decades due to inadequately controlled pollution. Persistent pesticides, chemical solvents and others tend to invade slowly the environment, to bioaccumulate in the food chain and to have long half-lives in animals and humans. During the past fifteen years, the scientific interest has been focused on xenoestrogens, i.e.,environmental chemicals with estrogen disrupting activity. Certain adverse health and reproductive outcomes are attributed to these chemicals in wildlife, in laboratory animals, as well as in humans. Although most toxic agents are hazardous in high doses, the human health risks associated with EDCs concern exposure to low doses. The human health risks that may be associated with these low-level but constant exposures are still largely unknown and highly controversial. In this paper, we review available data on environmental chemicals present in breast milk that may

  6. BreastDefend enhances effect of tamoxifen in estrogen receptor-positive human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Cheng, Shujie; Castillo, Victor; Welty, Matt; Alvarado, Mark; Eliaz, Isaac; Temm, Constance J; Sandusky, George E; Sliva, Daniel

    2017-02-16

    Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively. The molecular mechanism was identified using RNA microarray analysis and western blotting. Tumor tissues from xenograft mouse model were analyzed by immunohistochemistry. Our data clearly demonstrate that a combination of 4-hydroxytamoxifen (4-OHT) with BD lead to profound inhibition of cell proliferation and induction of apoptosis in MCF-7 cells. This effect is consistent with the regulation of apoptotic and TAM resistant genes at the transcription and translation levels. Importantly, TAM and BD co-treatment significantly enhanced apoptosis, suppressed tumor growth and reduced tumor weight in a xenograft model of human ER-positive breast cancer. BD sensitized ER-positive human breast cancer cells to 4-OHT/TAM treatment in vitro and in vivo. BreastDefend can be used in an adjuvant therapy to increase the therapeutic effect of tamoxifen in patients with ER-positive breast cancer.

  7. A Gene Regulatory Program in Human Breast Cancer.

    Science.gov (United States)

    Li, Renhua; Campos, John; Iida, Joji

    2015-12-01

    Molecular heterogeneity in human breast cancer has challenged diagnosis, prognosis, and clinical treatment. It is well known that molecular subtypes of breast tumors are associated with significant differences in prognosis and survival. Assuming that the differences are attributed to subtype-specific pathways, we then suspect that there might be gene regulatory mechanisms that modulate the behavior of the pathways and their interactions. In this study, we proposed an integrated methodology, including machine learning and information theory, to explore the mechanisms. Using existing data from three large cohorts of human breast cancer populations, we have identified an ensemble of 16 master regulator genes (or MR16) that can discriminate breast tumor samples into four major subtypes. Evidence from gene expression across the three cohorts has consistently indicated that the MR16 can be divided into two groups that demonstrate subtype-specific gene expression patterns. For example, group 1 MRs, including ESR1, FOXA1, and GATA3, are overexpressed in luminal A and luminal B subtypes, but lowly expressed in HER2-enriched and basal-like subtypes. In contrast, group 2 MRs, including FOXM1, EZH2, MYBL2, and ZNF695, display an opposite pattern. Furthermore, evidence from mutual information modeling has congruently indicated that the two groups of MRs either up- or down-regulate cancer driver-related genes in opposite directions. Furthermore, integration of somatic mutations with pathway changes leads to identification of canonical genomic alternations in a subtype-specific fashion. Taken together, these studies have implicated a gene regulatory program for breast tumor progression.

  8. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    Science.gov (United States)

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

    2014-03-01

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

  9. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  10. Analyzing the regulation of metabolic pathways in human breast cancer

    Directory of Open Access Journals (Sweden)

    Schramm Gunnar

    2010-09-01

    Full Text Available Abstract Background Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. Methods For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors. Results Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway. Conclusion We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.

  11. Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

    Directory of Open Access Journals (Sweden)

    Kamalidehghan Behnam

    2012-10-01

    Full Text Available Abstract Background Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research. Methods Two continuous human breast cell lines, designated MBC1 and MBC2, were successfully established and characterized from invasive ductal breast carcinoma tissues of Malaysian patients. MBC1 and MBC2 have been characterized in terms of morphology analysis, population doubling time, clonogenic formation, wound healing assay, invasion assay, cell cycle, DNA profiling, fluorescence immunocytochemistry, Western blotting and karyotyping. Results MBC1 and MBC2 exhibited adherent monolayer epithelial morphology at a passage number of 150. Receptor status of MBC1 and MBC2 show (ER+, PR+, HER2+ and (ER+, PR-, HER2+, respectively. These results are in discordance with histopathological studies of the tumoral tissues, which were triple negative and (ER-, PR-, HER2+ for MBC1 and MBC2, respectively. Both cell lines were capable of growing in soft agar culture, which suggests their metastatic potential. The MBC1 and MBC2 metaphase spreads showed an abnormal karyotype, including hyperdiploidy and complex rearrangements with modes of 52–58 chromosomes per cell. Conclusions Loss or gain in secondary properties, deregulation and specific genetic changes possibly conferred receptor changes during the culturing of tumoral cells. Thus, we hypothesize that, among heterogenous tumoral cells, only a small minority of ER+/PR+/HER2+ and ER+/PR-/HER2+ cells with lower energy metabolism might survive and adjust easily to in vitro conditions. These cell lines will pave the way for new perspectives in genetic and biological investigations, drug resistance and chemotherapy studies, and would serve as prototype models in Malaysian breast carcinogenesis investigations.

  12. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    Directory of Open Access Journals (Sweden)

    Sara Khalil

    Full Text Available Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS, and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001, consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04 and estrogen receptor-negative status (P = 0.03, both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%, similar to that in carcinomas (35%. Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%, suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02. Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary

  13. Benzyl Isothiocyanate Inhibits Epithelial-Mesenchymal Transition in Cultured and Xenografted Human Breast Cancer Cells

    OpenAIRE

    Sehrawat, Anuradha; Singh, Shivendra V.

    2011-01-01

    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells, and suppresses mammary cancer development in a transgenic mouse model. We now demonstrate, for the first time, that BITC inhibits epithelial-to-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell ...

  14. Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis

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    Dey Devaveena

    2009-12-01

    Full Text Available Abstract Background Recent studies have implicated aberrant Notch signaling in breast cancers. Yet, relatively little is known about the pattern of expression of various components of the Notch pathway, or its mechanism of action. To better understand the role of the Notch pathway in breast cancer, we have undertaken a detailed expression analysis of various Notch receptors, their ligands, and downstream targets at different stages of breast cancer progression. Results We report here that there is a general increase in the expression levels of Notch 1, 2, 4, Jagged1, Jagged2, and Delta-like 4 proteins in breast cancers, with simultaneous upregulation of multiple Notch receptors and ligands in a given cancer tissue. While Notch3 and Delta-like1 were undetectable in normal tissues, moderate to high expression was detected in several cancers. We detected the presence of active, cleaved Notch1, along with downstream targets of the Notch pathway, Hes1/Hes5, in ~75% of breast cancers, clearly indicating that in a large proportion of breast cancers Notch signaling is aberrantly activated. Furthermore, we detected cleaved Notch1 and Hes1/5 in early precursors of breast cancers - hyperplasia and ductal carcinoma in situ - suggesting that aberrant Notch activation may be an early event in breast cancer progression. Mechanistically, while constitutively active Notch1 alone failed to transform immortalized breast cells, it synergized with the Ras/MAPK pathway to mediate transformation. This cooperation is reflected in vivo, as a subset of cleaved Notch positive tumors additionally expressed phopsho-Erk1/2 in the nuclei. Such cases exhibited high node positivity, suggesting that Notch-Ras cooperation may lead to poor prognosis. Conclusions High level expression of Notch receptors and ligands, and its increased activation in several breast cancers and early precursors, places Notch signaling as a key player in breast cancer pathogenesis. Its cooperation with

  15. Engineering targeted chromosomal amplifications in human breast epithelial cells.

    Science.gov (United States)

    Springer, Simeon; Yi, Kyung H; Park, Jeenah; Rajpurohit, Anandita; Price, Amanda J; Lauring, Josh

    2015-07-01

    Chromosomal amplifications are among the most common genetic alterations found in human cancers. However, experimental systems to study the processes that lead to specific, recurrent amplification events in human cancers are lacking. Moreover, some common amplifications, such as that at 8p11-12 in breast cancer, harbor multiple driver oncogenes, which are poorly modeled by conventional overexpression approaches. We sought to develop an experimental system to model recurrent chromosomal amplification events in human cell lines. Our strategy is to use homologous-recombination-mediated gene targeting to deliver a dominantly selectable, amplifiable marker to a specified chromosomal location. We used adeno-associated virus vectors to target human MCF-7 breast cancer cells at the ZNF703 locus, in the recurrent 8p11-12 amplicon, using the E. coli inosine monophosphate dehydrogenase (IMPDH) enzyme as a marker. We applied selective pressure using IMPDH inhibitors. Surviving clones were found to have increased copy number of ZNF703 (average 2.5-fold increase) by droplet digital PCR and FISH. Genome-wide array comparative genomic hybridization confirmed that amplifications had occurred on the short arm of chromosome 8, without changes on 8q or other chromosomes. Patterns of amplification were variable and similar to those seen in primary human breast cancers, including "sawtooth" patterns, distal copy number loss, and large continuous regions of copy number gain. This system will allow study of the cis- and trans-acting factors that are permissive for chromosomal amplification and provide a model to analyze oncogene cooperativity in amplifications harboring multiple candidate driver genes.

  16. Carbon nanotube electron field emitters for X-ray imaging of human breast cancer

    OpenAIRE

    Gidcumb, Emily; Gao, Bo; Shan, Jing; Inscoe, Christy; Lu, Jianping; Zhou, Otto

    2014-01-01

    For imaging human breast cancer, digital breast tomosynthesis (DBT) has been shown to improve image quality and breast cancer detection in comparison to 2D mammography. Current DBT systems have limited spatial resolution and lengthy scan times. Stationary digital breast tomosynthesis (s-DBT), utilizing an array of carbon nanotube (CNT) field emission X-ray sources, provides increased spatial resolution and potentially faster imaging than current DBT systems. This study presents...

  17. Elevated MED28 expression predicts poor outcome in women with breast cancer

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    Horvath Steve

    2010-06-01

    Full Text Available Abstract Background MED28 (also known as EG-1 and magicin has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression. Methods Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed. Results MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death. Conclusions We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.

  18. 人乳头瘤病毒16/18感染、p53在女性乳腺浸润性导管癌中的表达及其相关性研究%The Expression and Correlation Studies of HPV16/18 Infection and p53 in Female with Breast Infiltrating Ductal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    洪亮; 杜玉开

    2011-01-01

    Objective To explore the expression and their relationship of HPV16/18 infection and p53 in female with breast infiltrating ductal carcinoma. Methods The expression level of HPV16/18 DNA and p53 in women breast infiltrating ductal carcinoma (n=45), breast fibroadenoma (n=20) and normal breast tissue (n=20) were detected with immunohistochemistry methods and PCR technology, respectively. Results HPV16/18 DNA and p53 protein expression rate in breast cancer group (51.1% and 46. 7%) were obviously higher than those in fibroadenoma group (15.0% and 10.0%) and normal breast group (5.0% and 0%) (P<0.01), and the expression rate of HPV16/18 UNA and p53 protein in the axillary lymph node metastasis was obviously higher than those without the axillary lymph node metastasis (P<0.05). With the increase of TMN, the expression rate of P53 protein increased significantly (P<0.05), HPV16/18 DNA and p53 protein expression was obviously positive correlated (r,=0.614,p<0.05). Conclusion HPV infection and p53 mutations participate jointly in the occurrence and development of female breast cancer, HPV infection may be the important factor for promoting p53 mutations.%目的 探讨人乳头瘤病毒(HPV) 16/18感染、p53在女性乳腺浸润性导管癌中的表达及其相互关系.方法 采用免疫组化方法和PCR技术,分别检测45例女性乳腺浸润性导管癌、20例乳腺纤维腺瘤及20例正常乳腺组织中HPV16/18DNA和p53表达水平.结果 乳腺癌组HPV 16/18 DNA和p53蛋白的表达率(51.1%和46.7%)明显高于乳腺纤维腺瘤组(15.0%和10.0%)和正常乳腺组(5.0%和0%),差异有显著性(P<0.01).有腋淋巴结转移者HPV 16/18DNA和p53蛋白的表达率明显高于无腋淋巴结转移癌者(P<0.05).随着TMN分期的升高,p53蛋白的表达率明显增加(P<0.05);HPV 16/18 DNA与p53蛋白的表达呈明显正相关(rs=0.614,P<0.05).结论 HPV感染和p53突变共同参与女性乳腺癌的发生和

  19. Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS stem/progenitor cell activity regardless of ErbB2 status.

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    Gillian Farnie

    Full Text Available Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal and SUM225 (ErbB2-overexpressing and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.

  20. Combined inhibition of ErbB1/2 and Notch receptors effectively targets breast ductal carcinoma in situ (DCIS) stem/progenitor cell activity regardless of ErbB2 status.

    Science.gov (United States)

    Farnie, Gillian; Willan, Pamela M; Clarke, Robert B; Bundred, Nigel J

    2013-01-01

    Pathways involved in DCIS stem and progenitor signalling are poorly understood yet are critical to understand DCIS biology and to develop new therapies. Notch and ErbB1/2 receptor signalling cross talk has been demonstrated in invasive breast cancer, but their role in DCIS stem and progenitor cells has not been investigated. We have utilised 2 DCIS cell lines, MCF10DCIS.com (ErbB2-normal) and SUM225 (ErbB2-overexpressing) and 7 human primary DCIS samples were cultured in 3D matrigel and as mammospheres in the presence, absence or combination of the Notch inhibitor, DAPT, and ErbB1/2 inhibitors, lapatinib or gefitinib. Western blotting was applied to assess downstream signalling. In this study we demonstrate that DAPT reduced acini size and mammosphere formation in MCF10DCIS.com whereas there was no effect in SUM225. Lapatinb reduced acini size and mammosphere formation in SUM225, whereas mammosphere formation and Notch1 activity were increased in MCF10DCIS.com. Combined DAPT/lapatinib treatment was more effective at reducing acini size in both DCIS cell lines. Mammosphere formation in cell lines and human primary DCIS was reduced further by DAPT/lapatinib or DAPT/gefitinib regardless of ErbB2 receptor status. Our pre-clinical human models of DCIS demonstrate that Notch and ErbB1/2 both play a role in DCIS acini growth and stem cell activity. We report for the first time that cross talk between the two pathways in DCIS occurs regardless of ErbB2 receptor status and inhibition of Notch and ErbB1/2 was more efficacious than either alone. These data provide further understanding of DCIS biology and suggest treatment strategies combining Notch and ErbB1/2 inhibitors should be investigated regardless of ErbB2 receptor status.

  1. Ultrasonic imaging and pathological features of encapsulated papillary carcinoma and ductal carcinoma in situ of breast%乳腺包膜内乳头状癌和乳腺导管原位癌的超声图像和病理特征分析

    Institute of Scientific and Technical Information of China (English)

    余燕民; 吕珏; 汪成; 徐明; 包家林

    2013-01-01

    目的 研究乳腺包膜内乳头状癌和乳腺导管原位癌的超声图像和病理特征.方法 回顾性分析7例乳腺包膜内乳头状癌和12例乳腺导管原位癌患者的资料,所有病例术前超声检查结果资料完整.采用HE染色观察肿瘤组织的病理学改变,免疫组织化学法检测雌激素受体(ER)、孕激素受体(PR)以及p53、Ki67、p63、CerbB-2蛋白的表达.结果 超声图像观察显示:乳腺包膜内乳头状癌组织形态不规则,边缘毛糙,内部回声为混合性回声,无回声区中见强回声,呈乳头状突起,后方回声增强,未见钙化灶,可见血流信号;乳腺导管原位癌组织中可见导管扩张或扩张的导管内见低回声,形态不规则,边缘毛糙,后方回声未增强,可见钙化灶和血流信号.HE染色后显微镜下显示:乳腺包膜内乳头状癌组织中可见纤细的纤维血管轴心,衬覆的肿瘤上皮细胞核为低或中等级别,外裹纤维囊;乳腺导管原位癌组织中可见上皮细胞呈肿瘤性增生和异型,其中乳头型乳腺导管原位癌组织中可见纤细的纤维血管轴心,无纤维囊.免疫组织化学检测显示:乳腺包膜内乳头状癌组织的上皮细胞中ER和PR均呈强阳性表达,p53、Ki67和CerbB-2均呈阴性或弱阳性表达,乳头内和病变周围肌上皮细胞中p63均呈阴性表达;乳腺导管原位癌的乳头内肌上皮细胞中p63呈阴性表达,而病变周围肌上皮细胞中p63呈阳性表达.结论 超声图像和病理学独特表现为乳腺包膜内乳头状癌和乳腺导管原位癌的诊断提供了帮助.%Objective To investigate the ultrasonic imaging and pathological features of encapsulated papillary carcinoma and ductal carcinoma in situ of breast.Methods The clinical data of 7 cases of encapsulated papillary carcinoma and 12 cases of ductal carcinoma in situ were retrospectively analysed,and there were preoperative ultrasonic findings and images for all cases.The pathological

  2. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

    In this paper,we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test,when require.We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps.Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper.In fact,features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue.We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent.

  3. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

    Science.gov (United States)

    Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

    2012-07-01

    Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

  4. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  5. Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    YAN Chen; TENG Zhi Ping; CHEN Yun Xin; SHEN Dan Hua; LI Jin Tao; ZENG Yi

    2016-01-01

    ObjectiveTo explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. MethodsPCR was used to screen HPV16 and HPV18 oncogenesE6 andE7 in the SKBR3 cell line andin 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18E6 andE7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. ResultsHPV18 oncogenesE6 andE7 were amplified and sequenced from the SKBR3 cells. Ofthe patient samples, 6.58% and 23.68% were tested to bepositivefor HPV18E6 and HPV18E7. In the cell culture models, the knockdown of HPV18E6 andE7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. ConclusionHPV was a contributor to virus causedhuman breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.

  6. Mathematical analysis of mammary ducts in lactating human breast.

    Science.gov (United States)

    Mortazavi, S Negin; Geddes, Donna; Hassiotou, Foteini; Hassanipour, Fatemeh

    2014-01-01

    This work studies a simple model for milk transport through lactating human breast ducts, and describes mathematically the mass transfer from alveolar sacs through the mammary ducts to the nipple. In this model both the phenomena of diffusion in the sacs and conventional flow in ducts have been considered. The ensuing analysis reveals that there is an optimal range of bifurcation numbers leading to the easiest milk flow based on the minimum flow resistance. This model formulates certain difficult-to-measure values like diameter of the alveolar sacs, and the total length of the milk path as a function of easy-to-measure properties such as milk fluid properties and macroscopic measurements of the breast. Alveolar dimensions from breast tissues of six lactating women are measured and reported in this paper. The theoretically calculated alveoli diameters for optimum milk flow (as a function of bifurcation numbers) show excellent match with our biological data on alveolar dimensions. Also, the mathematical model indicates that for minimum milk flow resistance the glandular tissue must be within a short distance from the base of the nipple, an observation that matches well with the latest anatomical and physiological research.

  7. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  8. Histological and immunohistochemical identification of atypical ductal mammary hyperplasia as a preneoplastic marker in dogs.

    Science.gov (United States)

    Ferreira, E; Gobbi, H; Saraiva, B S; Cassali, G D

    2012-03-01

    This study describes and evaluates the morphological and molecular relationship between canine mammary ductal hyperplasias with atypia and canine mammary neoplasias. Ductal hyperplasia was identified in association with malignant neoplasia in 56 of the 115 cases (48,8%), and although ductal hyperplasia without atypia was the type most frequently noted in the cases, most examples of hyperplasia with atypia were associated with mammary tumors. Estrogen receptor, E-cadherin, and cytokeratins 1, 5, 10 and 14 (CK34bE12) expression was quite lower than in normal mammary tissue, and HER2 overexpression was absent in all proliferative cells of ductal hyperplasia. The Ki-67 expression, epidermal growth factor receptor and progesterone receptor expression appeared higher in those hyperplastic lesions analyzed than in normal mammary glands. These findings suggest that canine mammary atypical hyperplasia may play an important role in the process of malignant neoplastic transformation, with molecular alterations that are similar to precursor lesions reported in humans.

  9. [Breast ductoscopy].

    Science.gov (United States)

    Sharon, Eran; Avin, Ilan D; Leong, Wey

    2011-02-01

    The majority of benign and malignant breast diseases originate in the ductal system. Breast ductoscopy (BD) allows direct access to this ductal system and thus holds great promise in the diagnosis and surgical management of a number of breast diseases. BD was first developed over 20 years ago to investigate nipple discharge. Indeed, till now, this remains the most common indication. However, BD technology has been further developed for a variety of new clinical applications. For example, BD-guided ductal ravage combined with molecular and genetic analysis can be a powerful screening tool for women at high-risk of breast cancer. BD can also be used during lumpectomy to identify additional radiographically occult disease. This refined intraoperative margin assessment can help surgeons to achieve clear margins at the first excision while optimizing the extent of resection. In the future, this same precise intraoperative margin assessment may facilitate a variety of local ablative techniques including laser Over time, BD is likely to evolve beyond its current technological limitations to realize its full diagnostic and therapeutic potential. The article describes the technique of BD, reviews its evolution and discusses current and future applications.

  10. Sustained co-cultivation with human placenta-derived MSCs enhances ALK5/Smad3 signaling in human breast epithelial cells, leading to EMT and differentiation.

    Science.gov (United States)

    Yoo, Young A; Kang, Myoung Hee; Kim, Byung Soo; Kim, Jun Suk; Seo, Jae Hong

    2009-06-01

    The interaction between mammary epithelial cells and their surrounding microenvironment are important in the development of the mammary gland. Thus, mesenchymal stem cells (MSCs), which retain pluripotency for various mesenchymal lineages, may provide a permissive environment for the morphologic alteration and differentiation of mammary epithelial cells. To this end, we investigated whether the interactions between mammary epithelial cells and human placenta-derived MSCs (hPMSC) affect the morphology, proliferation, and differentiation of epithelial cells in a co-culture system. We show that after co-culture with hPMSCs, human mammary epithelial cell lines (MCF-10F and HEMC) underwent significant morphologic alterations and a dramatic increase in ductal-alveolar branching, which was accompanied by a decrease or loss of the epithelial marker E-cadherin and a gain of the mesenchymal markers, alpha-SMA and vimentin. MCF-10F and HEMC proliferation was also inhibited in the presence of hPMSCs, and this retardation in growth was due to cell cycle arrest. Furthermore, in MCF-10F and HMEC cells, hPMSCs induced the production of lipid droplets, milk fat globule protein, and milk protein lactoferrin, which are markers of functional mammary differentiation. We also noticed an elevation in ALK5 and phosphorylated Smad3 protein levels upon hPMSC co-culture. Strikingly, the changes in morphology, proliferation, and differentiation were reversed by treatment with ALK5 or Smad3 knockdown in MCF-10F/hPMSC co-cultures. Collectively, our findings suggest that co-cultivation with hPMSCs leads to epithelial to mesenchymal transition (EMT) and differentiation of human breast epithelial cells through the ALK5/Smad3 signaling pathway.

  11. High risk human papillomavirus and Epstein Barr virus in human breast milk

    Directory of Open Access Journals (Sweden)

    Glenn Wendy K

    2012-09-01

    Full Text Available Abstract Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid and in situ polymerase chain reaction (PCR techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15% from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%. Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.

  12. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  13. Relation between radiographic BI-RADS scores and triple negativity in patients with ductal carcinomas.

    Science.gov (United States)

    Oktay, Murat; Oktay, Nilay Aydın; Besir, Fahri Halit; Buyukkaya, Ramazan; Erdem, Havva; Onal, Binnur; Ozaydın, Ismet; Yazıcı, Burhan

    2014-01-01

    The aim of this study was to investigate association of radiographic (BI-RADS 4 and 5) results and prognostic factors of invasive ductal carcinomas with their histopathological subtypes. A total of 103 patients histopathologically diagnosed with invasive ductal carcinoma of breast with in last five years period were enrolled. Of them, 69 patients who had radiological reports in were included from registry of Radiology Department; Duzce University Training and Research Hospital archives. BI-RADS scores (4 and 5) of radiological reports and subtypes of ductal carcinoma were compared. Of 69 cases, 12 of 22 cases with BIRADS 4 score were Triple negative (TN) while 5 of 47 cases with BIRADS 5 score were TN (p = 0.001). The patients with TN tumors were found to have lower average age, higher grade, higher Ki67 proliferative index and fewer lymph node metastasis than those with non-TN ductal carcinomas (p = 0.048; 0.019; 0.02; 0.048 respectively). Patients who had radiological BIRADS 4 score were significantly more frequent TN type carcinoma than BI-RADS 5. It is important to pay attention to this issue when clinicians evaluate patients with BI-RADS 4 score breast lesions.

  14. Role of KCNMA1 in breast cancer.

    Directory of Open Access Journals (Sweden)

    Martin Oeggerli

    Full Text Available KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+-activated (BK potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3-7%. We performed an extensive analysis on breast cancer tissue microarrays (TMA of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.

  15. [Immunohistochemical research on human breast tumors using monoclonal antibodies to intermediate filament proteins. Cancer of the breast].

    Science.gov (United States)

    Gel'shteĭn, V I; Chipysheva, T A; Ermilova, V D; Litvinova, L V; Bannikov, G A

    1986-01-01

    Immunomorphologic study of 29 breast cancer cases using monoclonal antibodies to proteins of intermediate filaments shown to differentiate the lining epithelium from myoepithelium in the non-proliferating epithelial structures of the mamma, has shown the cells in the majority of tumours (according to the International WHO Classification defined as infiltrating ductal, lobular, and tubular cancer forms) to contain prekeratin (PK) C12, specific for normal lining epithelium, but not for the myoepithelium. In cases of cancer with chondroid metaplasia (a malignant variant of the so-called "mixed tumour") the cells contained PK E3, vimentin and structural myosin, normally specific for myoepithelium. The cell heterogenicity in PK C12 content or its absence noted in the infiltrating cancers with predominance of a solid component can indicate a high degree of tumour anaplasia. It is concluded that usage of monoclonal antibodies to PK C12, invariably found in the cells of fibrotic invasion foci, can be a useful indicator for early diagnosis of infiltrative tumour growth.

  16. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    Science.gov (United States)

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

  17. Expressions and significance of VEGF-C and CXCR4 in breast infiltrating ductal carcinoma%VEGF-C、CXCR4在乳腺浸润性导管癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    杜宏道; 盛薇; 高希涛; 张倩

    2012-01-01

    Objective To investigate the expressions of vascular endothelial growth factor-C (VEGF-C) and chemokines receptor-4 (CXCR4) in breast infiltrating carcinoma and breast fibroadenoma tissues as well as the relationship of lymphatic metastasis and prognosis with breast carcinoma. Methods The expressions of VEGF-C and CXCR4 were detected by immunohistochemical method in 72 cases of breast infiltrating carcinoma and 15 cases of breast fibroadenoma tissues. Results The positive rate of VEGF-C and CXCR4 in breast carcinoma was 76.4% and 58. 3%, respectively. The level of VEGF-C and CXCR4 expressions was significantly higher in breast infiltrating carcinoma than in breast fibroadenoma tissues (P0.05). Conclusion VEGF-C and CXCR4 may play a crucial role in lymphatic vessel invasion and lymph node metastasis in breast cancer.%目的 分析血管内皮生长因子-C(VEGF-C)、趋化因子受体-4(CXCR4)在乳腺浸润性导管癌组织及乳腺纤维腺瘤组织中的表达,探讨其与淋巴管生成、乳腺癌的淋巴转移的关系.方法 应用免疫组织化学方法检测72例乳腺癌组织、15例乳腺纤维腺瘤中VEGF-C、CXCR4的表达.结果 72例乳腺癌组织中VEGF-C、CXCR4的表达率分别为76.4%、58.3%,显著高于乳腺纤维腺瘤组织(20%、13.3%),差异有统计学意义(P<0.01).VEGF-C、CXCR4的表达与患者的年龄、肿瘤大小、雌孕激素受体(ER、PR)的表达无关(P>0.05),而与组织学分级、临床分期、淋巴管的浸润及淋巴结转移有关(P<0.01).结论 VEGF-C、CXCR4在介导乳腺癌细胞淋巴管浸润及淋巴结转移中可能起重要协同作用.

  18. Histological analysis of gamma delta T lymphocytes infiltrating human triple-negative breast carcinomas

    Directory of Open Access Journals (Sweden)

    Jose Villacorta Hidalgo

    2014-12-01

    Full Text Available Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic and prognostic factors. Triple-negative breast cancers (TNBCs lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs are somewhat less frequent. Infiltrating T cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T cells within CD3+ tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infitrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T cells were higher in MBCs than in IDCs. γδ T cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient’s prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T cells at the molecular and functional level are in progress.

  19. Histological Analysis of γδ T Lymphocytes Infiltrating Human Triple-Negative Breast Carcinomas.

    Science.gov (United States)

    Hidalgo, Jose Villacorta; Bronsert, Peter; Orlowska-Volk, Marzenna; Díaz, Liliana B; Stickeler, Elmar; Werner, Martin; Schmitt-Graeff, Annette; Kayser, Gian; Malkovsky, Miroslav; Fisch, Paul

    2014-01-01

    Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic, and prognostic factors. Triple-negative breast carcinomas (TNBCs) lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs) with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs) are somewhat less frequent. Infiltrating T-cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T-cells within CD3(+) tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs, and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infiltrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T-cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T-cells were higher in MBCs than in IDCs. γδ T-cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T-cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient's prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T-cells at the molecular and functional level are in progress.

  20. 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.

  1. 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 ana

  2. B7-H4基因多态性与乳腺浸润性导管癌预后的相关性研究%Relationship between the polymorphisms of B7-H4 gene and the prognosis of breast infiltrative ductal carcinoma in Chinese Han females

    Institute of Scientific and Technical Information of China (English)

    李大林; 章婕; 傅振坤; 许凤燕; 李殿俊

    2010-01-01

    目的 探讨B7-H4基因rs10754339、rs10801935和rs3738414等单核苷酸多态性(SNP)位点多态性与黑龙江省妇女乳腺浸润性导管癌预后的相关性.方法 取280例乳腺浸润性导管癌患者的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行B7-H4单核苷酸多态性检测,引用统计学软件分析基因多态性与患者临床指标(包括肿瘤大小,淋巴结转移,以及雌激素受体、孕激素受体和P53基因的表达)间的关系(卡方检验计算P值),进而确定该基因与黑龙江省汉族妇女乳腺癌预后的相关性.结果 B7-H4基因的rs10754339中,AA和AG基因型发生频率在雌激素受体表达阳性和阴性患者中有统计学差异(χ~2=4.06,P<0.05;χ~2=3.97,P<0.05),AA基因型和G等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异(χ~2=4.74,P<0.05;χ~2=5.30,P<0.05).rs10801935中,AA基因型和C等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异(χ~2=5.36,P<0.05;χ~2=5.90,P<0.05),而AC基因型发生频率在P53基因表达阳性和阴性患者中有显著差异(χ~2=5.82,P<0.05).结论 B7-H4基因多态性与乳腺浸润性导管癌患者雌激素受体,孕激素受体及P53基因的表达有关联,与乳腺癌患者的预后有一定相关性.%Objective To investigate the association between the polymorphisms of B7-H4 gene (in cluding rsl0754339, rs10801935 and rs3738414) and the prognosis of infiltrating ductal carcinoma in Chinese women of Heilongjiang province. Methods Two hundreds and eighty Chinese females with infiltrative ductal carcinoma were included in the study. The single nucleotide polymorphisms (SNPs) of rsl0754339, rsl0801935 and rs3738414 in B7-H4 gene were genotyped by PCR-RFLP. The association of the SNPs of B7 H4 gene with the clinical features of breast infiltrating ductal carcinoma (including tumor size, lymph node in volvement , and the expression status

  3. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

    Science.gov (United States)

    Barr, L; Metaxas, G; Harbach, C A J; Savoy, L A; Darbre, P D

    2012-03-01

    The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

  4. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.;

    2006-01-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5%...

  5. Temporal Changes of Human Breast Milk Lipids of Chinese Mothers

    Directory of Open Access Journals (Sweden)

    Francesca Giuffrida

    2016-11-01

    Full Text Available Fatty acids (FA, phospholipids (PL, and gangliosides (GD play a central role in infant growth, immune and inflammatory responses. The aim of this study was to determine FA, PL, and GD compositional changes in human milk (HM during lactation in a large group of Chinese lactating mothers (540 volunteers residing in Beijing, Guangzhou, and Suzhou. HM samples were collected after full expression from one breast and while the baby was fed on the other breast. FA were assessed by direct methylation followed by gas chromatography (GC analysis. PL and GD were extracted using chloroform and methanol. A methodology employing liquid chromatography coupled with an evaporative light scattering detector (ELSD and with time of flight (TOF mass spectrometry was used to quantify PL and GD classes in HM, respectively. Saturated FA (SFA, mono-unsaturated FA (MUFA, and PL content decreased during lactation, while polyunsaturated FA (PUFA and GD content increased. Among different cities, over the lactation time, HM from Beijing showed the highest SFA content, HM from Guangzhou the highest MUFA content and HM from Suzhou the highest n-3PUFA content. The highest total PL and GD contents were observed in HM from Suzhou. In order to investigate the influence of the diet on maternal milk composition, a careful analyses of dietary habits of these population needs to be performed in the future.

  6. Expression of Axl and its prognostic significance in human breast cancer

    OpenAIRE

    Jin, Gaoyuan; Wang, Zhenzhen; Wang, Jianguang; Zhang, Like; CHEN Yanbin; Yuan, Pengfei; Liu, Dechun

    2016-01-01

    Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 ...

  7. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita

    2010-08-01

    Full Text Available Abstract Background Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1ΔR on radiosensitization of human breast cancer cells. Methods The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1ΔR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation. Results Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1ΔR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells. Conclusion Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.

  8. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing, E-mail: wangstella5@163.com [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Yang, Qifeng, E-mail: qifengy@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Haffty, Bruce G., E-mail: hafftybg@umdnj.edu [Department of Radiation Oncology, UMDNJ-Robert Wood Johnson School of Medicine, Cancer Institute of New Jersey, NB (United States); Li, Xiaoyan, E-mail: xiaoyanli1219@gmail.com [Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Moran, Meena S., E-mail: meena.moran@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2013-02-08

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

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

    OpenAIRE

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

    2014-01-01

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

  10. The B7-H1 (PD-L1 T Lymphocyte-Inhibitory Molecule Is Expressed in Breast Cancer Patients with Infiltrating Ductal Carcinoma: Correlation with Important High-Risk Prognostic Factors

    Directory of Open Access Journals (Sweden)

    Hazem Ghebeh

    2006-03-01

    Full Text Available B7-H1 molecule increases the apoptosis of tumorreactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells, but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%. Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade IIInegative (P = .012, estrogen receptor-negative (P = .036, and progesterone receptor-negative (P = .040 patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042, histologic grade III (P=.015, positivity of Her2/neu status (P=.019, and severe tumor lymphocyte infiltration (P = .001. Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

  11. The B7-H1 (PD-L1)T Lymphocyte-Inhibitory Molecule Is Expressed in Breast Cancer Patients with Infiltrating Ductal Carcinoma: Correlation with Important High-Risk Prognostic Factors1

    Science.gov (United States)

    Ghebeh, Hazem; Mohammed, Shamayel; Al-Omair, Abeer; Qattan, Amal; Lehe, Cynthia; Al-Qudaihi, Ghofran; Elkum, Naser; Alshabanah, Mohamed; Amer, Suad Bin; Tulbah, Asma; Ajarim, Dahish; Al-Tweigeri, Taher; Dermime, Said

    2006-01-01

    Abstract B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule. PMID:16611412

  12. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors.

    Science.gov (United States)

    Ghebeh, Hazem; Mohammed, Shamayel; Al-Omair, Abeer; Qattan, Amal; Lehe, Cynthia; Al-Qudaihi, Ghofran; Elkum, Naser; Alshabanah, Mohamed; Bin Amer, Suad; Tulbah, Asma; Ajarim, Dahish; Al-Tweigeri, Taher; Dermime, Said

    2006-03-01

    B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

  13. Preoperative diagnosis of ductal carcinoma in situ arising within a mammary fibroadenoma: a case report.

    Science.gov (United States)

    Ooe, Asako; Takahara, Sachiko; Sumiyoshi, Kazuhiro; Yamamoto, Hitoshi; Shiba, Eiichi; Kawai, Jun

    2011-07-01

    Fibroadenoma is the most common form of benign breast tumor and the most common breast tumor in women under 30 years of age. However, carcinoma arising within a fibroadenoma is unusual, with over 100 cases reported in the literature. Histological diagnosis is typically unexpected. A 46-year-old female with no family history of breast malignancies was admitted for an elastic hard lump in the upper-outer quadrant of her right breast. At a clinic that she visited previously, her condition was diagnosed by core needle biopsy with four specimens showing fibroadenoma with borderline atypical ductal hyperplasia at pathology. Excisional biopsy was recommended for pathological diagnosis. The patient requested a definitive diagnosis and alternative treatment to tumorectomy. More biopsy specimens were needed for pathological diagnosis; therefore, ultrasonography-guided vacuum-assisted core needle biopsies were obtained, confirming ductal carcinoma in situ with questionable microinvasion of intracanalicular- and pericanalicular-type fibroadenoma. Right breast-conserving surgery and sentinel lymph node biopsy were immediately performed for radical therapy. We present this case to increase awareness of this entity and stress the need for histological evaluation of some breast masses.

  14. Penurunan Imunoekspresi P63 Pada Mioepitel Ductal Carcinoma In Situ (DCIS Payudara Sebagai Prediktor Infiltrasi Tumor

    Directory of Open Access Journals (Sweden)

    Teresa Liliana Wargasetia

    2009-03-01

    Full Text Available The occurrence of breast carcinoma is common in women. Ductal carcinoma in situ (DCIS of the breast is breast carcinoma with tumor cells which exist in the breast glandular duct and have not infiltrated into stroma. Retrospective study has been made on 23 paraffin blocks of morphological breast DCIS variants, namely kribriform, solid, and komedo. One way to find out DCIS aggressiveness is by detecting myoepithelial cells surrounding the breast duct indicating the integrity of the basal membrane. Detection of myoepithelial cells by means of immunohistochemical technique is done by using a selective marker for breast myoepithelial cells, namely p63. The aim of this research was predict tumor infiltration through decrease of immunoexpression of p63 in myoepithelial cells of morphological variants: cibriform, solid, and komedo of breast DCIS. This research was performed at Pathology Anatomy Laboratory of Medical Faculty of Padjadjaran University/RSUP Hasan Sadikin Bandung from Juli 2005 to September 2006. The result of the research indicated that immunoexpression of p63 in myoepithelial cells of morphological breast DCIS variants - cibriform, solid and komedo - did not show any significant difference (p<: 0,05. This indicated that tumor infiltration can occur in every breast DCIS morphological variant being studied, namely cribriform, solid, and comedo. The conclusion of this research is that decrease of immunoexpression of p63 in myoepithelial cells of morphological variants: cibriform, solid, and comedo of breast DCIS predict the presence of tumor infiltration.

  15. 乳腺叶状肿瘤并导管内癌及混合性浸润性导管癌伴产生软骨基质的癌一例病理分析及文献复习%Phyllodes tumor, intraductal carcinoma, mixed invasive ductal carcinoma, and metaplastic carcinoma producing cartilage matrix of breast:a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    秦珍珠; 张玉文; 王丹; 窦颖; 邱晓娣

    2016-01-01

    目的 探讨叶状肿瘤并导管上皮癌变的临床病理特征.方法 综合分析研究1例叶状肿瘤并上皮成分癌变患者的临床资料、大体图像、HE形态、免疫组化特征及会诊资料等,了解该肿瘤的病理特征.结果 患者为叶状肿瘤并导管内癌及混合性浸润性导管癌产生软骨基质的癌.结论 叶状肿瘤可以伴有导管内癌,甚至是浸润性癌.按规范要求,对较大肿瘤多取材,小标本全部取材,结合免疫组化等检查及会诊有助于少见肿瘤病理类型的发现与诊断.%Objective To investigate the clinical and pathological features of phyllodes tumors and ductal epithelial canceration.Methods The clinical data,general picture,HE morphological,immunohistochemical features,and consultation information of one patient with phyllodes tumors and ductal epithelial canceration was studied,in order to understand the characteristics of the tumor.Results The case was phyllodes tumor,intraductal carcinoma,mixed invasive ductal carcinoma,and metaplastic carcinoma producing cartilage matrix of breast.Conclusions Phyloodes tumors can be with intraducatal carcinoma,even invasive cancer.For larger tumors,pathologic sampling even whole serial sections combined with immunohistochemistry examination and consultation can help find rare tumor types.

  16. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Klijn Jan GM

    2009-07-01

    Full Text Available Abstract Background Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Methods Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. Results The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. Conclusion The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines.

  17. Ductal Carcinoma in Situ (DCIS)

    Science.gov (United States)

    ... you're diagnosed in the first trimester of pregnancy, you've received prior radiation to your chest or breast, or you have a condition that makes you more sensitive to the side effects of radiation therapy, such as systemic lupus erythematosus. You prefer to have a mastectomy rather than ...

  18. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  19. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer.

    Science.gov (United States)

    Cotter, Kristina; Liberman, Rachel; Sun-Wada, GeHong; Wada, Yoh; Sgroi, Dennis; Naber, Stephen; Brown, Dennis; Breton, Sylvie; Forgac, Michael

    2016-07-19

    The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. Previous work has demonstrated that plasma membrane V-ATPases are important for breast cancer invasion in vitro and that the V-ATPase subunit a isoform a3 is upregulated in and critical for MDA-MB231 and MCF10CA1a breast cancer cell invasion. It has been proposed that subunit a3 is present on the plasma membrane of invasive breast cancer cells and is overexpressed in human breast cancer. To test this, we used an a3-specific antibody to assess localization in breast cancer cells. Subunit a3 localizes to the leading edge of migrating breast cancer cells, but not the plasma membrane of normal breast epithelial cells. Furthermore, invasive breast cancer cells express a3 throughout all intracellular compartments tested, including endosomes, the Golgi, and lysosomes. Moreover, subunit a3 knockdown in MB231 breast cancer cells reduces in vitro migration. This reduction is not enhanced upon addition of a V-ATPase inhibitor, suggesting that a3-containing V-ATPases are critical for breast cancer migration. Finally, we have tested a3 expression in human breast cancer tissue and mRNA prepared from normal and cancerous breast tissue. a3 mRNA was upregulated 2.5-47 fold in all breast tumor cDNA samples tested relative to normal tissue, with expression generally correlated to cancer stage. Furthermore, a3 protein expression was increased in invasive breast cancer tissue relative to noninvasive cancer and normal breast tissue. These studies suggest that subunit a3 plays an important role in invasive human breast cancer.

  20. Coexistence of lobular granulomatous mastitis and ductal carcinoma: a fortuitous association?

    Science.gov (United States)

    Limaiem, F; Khadhar, A; Hassan, F; Bouraoui, S; Lahmar, A; Mzabi, S

    2013-12-01

    A 77-year-old female patient with a medical history significant for hypertension and epilepsy presented with right breast pain of 6-months duration. Examination revealed a hard sub-areola tender mass with irregular borders associated with mild right nipple retraction. Mammography showed a 2.2 x 2.4 cm stellate mass of the right breast. Ultrasound-guided core biopsies of the tumour were performed. Pathological examination revealed a grade II infiltrating ductal carcinoma. The patient underwent right radical mastectomy with homolateral axillary lymphadenectomy. Histological examination of the surgical specimen revealed grade II infiltrating ductal carcinoma concomitant with granulomatous lobular mastitis. To the best of our knowledge, the coexistence of granulomatous lobular mastitis and ductal carcinoma has been described only twice in the English language literature. The theory that chronic inflammation leads to cancer is well documented. Whether our patient had developed cancer from granulomatous lobular mastitis or otherwise is a matter of debate until more cases are encountered and more research is done in the area of breast cancer pathogenesis with regards to it arising from granulomatous lobular mastitis.

  1. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    OpenAIRE

    James Ryan; Curran, Catherine E.; Emer Hennessy; John Newell; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M

    2011-01-01

    INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), t...

  2. Pancreatic ductal adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia:repor t of a case

    Institute of Scientific and Technical Information of China (English)

    Rajkumar Krishnasamy; Shaleen Agarwal; Shivendra Singh; Sunil Puri; Puja Sakhuja; Anil K Agarwal

    2007-01-01

    BACKGROUND:The presence of pancreatic ductal intraepithelial neoplasia in patients with chronic pancreatitis is a risk factor for development of pancreatic adenocarcinoma. METHOD: A case of pancreatic ductal adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia was diagnosed in the setting of chronic pancreatitis. RESULTS:Distal pancreatectomy combined with splenec-tomy was performed with a diagnosis of pancreatic body carcinoma. Histopathological examination suggested adenocarcinoma associated with pancreatic ductal intraepithelial neoplasia. The tumor was detected in the remaining head of the pancreas, for which a total pancreatectomy was done. CONCLUSIONS: When a patient with pancreatic ductal intraepithelial neoplasia associated with adenocarcinoma of the pancreas in the setting of chronic pancreatitis is at an increased risk of recurrence in the remaining pancreatic parenchyma, total pancreatectomy may be feasible.

  3. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation.

    Science.gov (United States)

    Duo, Jian; Ying, Guo-Guang; Wang, Guo-Wen; Zhang, Li

    2012-06-01

    Breast cancer is a disease in which cancer cells form in the tissues of the breast. The present study aimed to explore the effect of the flavonoid compound quercetin on the growth and apoptosis of human breast cancer cells. Varying concentrations (12.5, 25, 50, 100, 200 µM) of quercetin were applied to cultured MCF-7 human breast cancer cells for defined lengths of time. At 50 to 200 µM doses, quercetin significantly inhibited the proliferation of MCF-7 cells assessed by MTT colorimetry, in both dose- and time-dependent manners (Papoptosis after 48 h of exposure (Pquercetin treatment Bcl-2 expression decreased significantly while Bax expression increased significantly (Pquercetin inhibits cell growth and induces apoptosis in MCF-7 human breast cancer cells. The mechanisms behind these effects may stem from the downregulation of Bcl-2 protein expression and upregulation of Bax expression.

  4. Specific binding of benzodiazepines to human breast cancer cell lines.

    Science.gov (United States)

    Beinlich, A; Strohmeier, R; Kaufmann, M; Kuhl, H

    1999-01-01

    Binding of [3H]Ro5-4864, a peripheral benzodiazepine receptor (PBR) agonist, to BT-20 human, estrogen- (ER) and progesterone- (PR) receptor negative breast cancer cells was characterized. It was found to be specific, dose-dependent and saturable with a single population of binding sites. Dissociation constant (K(D)) was 8.5 nM, maximal binding capacity (Bmax) 339 fM/10(6) cells. Ro5-4864 (IC50 17.3 nM) and PK 11195 (IC50 12.3 nM) were able to compete with [3H]Ro5-4864 for binding, indicating specificity of interaction with PBR. Diazepam was able to displace [3H]Ro5-4864 from binding only at high concentrations (>1 microM), while ODN did not compete for PBR binding. Thymidine-uptake assay showed a biphasic response of cell proliferation. While low concentrations (100 nM) of Ro5-4864, PK 11195 and diazepam increased cell growth by 10 to 20%, higher concentrations (10-100 microM) significantly inhibited cell proliferation. PK 11195, a potent PBR ligand, was able to attenuate growth of BT-20 cells stimulated by 100 nM Ro5-4864 and to reverse growth reduction caused by 1 and 10 microM Ro5-4864, but not by 50 microM and 100 microM. This indicates that the antimitotic activity of higher concentrations of Ro5-4864 is independent of PBR binding. It is suggested, that PBR are involved in growth regulation of certain human breast cancer cell lines, possibly by supplying proliferating cells with energy, as their endogenous ligand is a polypeptide transporting Acyl-CoA.

  5. Volatile organic metabolites identify patients with breast cancer, cyclomastopathy, and mammary gland fibroma.

    Science.gov (United States)

    Wang, Changsong; Sun, Bo; Guo, Lei; Wang, Xiaoyang; Ke, Chaofu; Liu, Shanshan; Zhao, Wei; Luo, Suqi; Guo, Zhigang; Zhang, Yang; Xu, Guowang; Li, Enyou

    2014-06-20

    The association between cancer and volatile organic metabolites in exhaled breaths has attracted increasing attention from researchers. The present study reports on a systematic study of gas profiles of metabolites in human exhaled breath by pattern recognition methods. Exhaled breath was collected from 85 patients with histologically confirmed breast disease (including 39 individuals with infiltrating ductal carcinoma, 25 individuals with cyclomastopathy and from 21 individuals with mammary gland fibroma) and 45 healthy volunteers. Principal component analysis and partial least squares discriminant analysis were used to process the final data. The volatile organic metabolites exhibited significant differences between breast cancer and normal controls, breast cancer and cyclomastopathy, and breast cancer and mammary gland fibroma; 21, 6, and 8 characteristic metabolites played decisive roles in sample classification, respectively (P fibroma patients, and patients with cyclomastopathy (P < 0.05). The identified three volatile organic metabolites associated with breast cancer may serve as novel diagnostic biomarkers.

  6. Human Progesterone A-Form as a Target for New Drug Discovery in Human Breast Cancer

    Science.gov (United States)

    2001-07-01

    Voltz et al’(ii 3 altered recycling, and impaired regulation of the PDGFR TR4 chloride transporter by hormones. Most recent studies suggest that CFTR ...growth transporters, and other proteins localized at or near the factor receptor and ion transporters such as CFTR , plasma membrane. Consistent with this...overexpression in human breast cancers cytoskeleton. This review will focus on the signaling and mutations in NHERF targets, such as CFTR and paradigms

  7. DNA Replication Licensing and Progenitor Numbers Are Increased by Progesterone in Normal Human Breast

    NARCIS (Netherlands)

    Graham, J. Dinny; Mote, Patricia A.; Salagame, Usha; van Dijk, Jessica H.; Balleine, Rosemary L.; Huschtscha, Lily I.; Reddel, Roger R.; Clarke, Christine L.

    2009-01-01

    Proliferation in the nonpregnant human breast is highest in the luteal phase of the menstrual cycle when serum progesterone levels are high, and exposure to progesterone analogues in hormone replacement therapy is known to elevate breast cancer risk, yet the proliferative effects of progesterone in

  8. The nude mouse as an in vivo model for human breast cancer invasion and metastasis

    DEFF Research Database (Denmark)

    Brünner, N; Boysen, B; Rømer, J;

    1993-01-01

    Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains...

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

    Science.gov (United States)

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

    2014-03-01

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

  10. Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

    Directory of Open Access Journals (Sweden)

    I-Hsuan Lin

    Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

  11. Imaging of precursor lesions of the female breast; Bildgebung und Vorgehen bei praeinvasiven Laesionen der Mamma

    Energy Technology Data Exchange (ETDEWEB)

    Weigel, Stefanie [Universitaetsklinikum Muenster (Germany). Inst. fuer Klinische Radiologie; Universitaetsklinikum Muenster (Germany). Referenzzentrum Mammografie; Decker, Thomas [Dietrich-Bonhoeffer-Klinikum Neubrandenburg, Neubrandenburg (Germany). Inst. fuer Pathologie; Heindel, Walter [Universitaetsklinikum Muenster (Germany). Referenzzentrum Mammografie; Muenster Univ. (Germany). Medizinische Fakultaet

    2012-06-15

    Precursor lesions of the breast are biologically and clinically heterogeneous neoplastic lesions with a varying risk for progression to an invasive breast cancer. This review presents definitions, diagnostic criteria and concepts for the clinical management of the following lesions: ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), lobular neoplasia (LN). (orig.)

  12. Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice

    DEFF Research Database (Denmark)

    Almholt, Kasper; Nielsen, Boye Schnack; Frandsen, Thomas Leth;

    2003-01-01

    of metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth...... limiting for tumor vascularization and metastasis, or that there is a functional redundancy between PAI-1 and other inhibitors of the uPA/plasmin system, masking the effect of PAI-1 deficiency....

  13. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.

    Directory of Open Access Journals (Sweden)

    Chen Wang

    Full Text Available A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.To study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.The co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.

  14. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaolan, E-mail: huxiaolan1998@yahoo.com.cn [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Zhang, Xianqi [The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou (China); Qiu, Shuifeng [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Yu, Daihua; Lin, Shuxin [Fourth Military Medical University, Xi' an (China)

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  15. Feature Extraction and Analysis of Breast Cancer Specimen

    Science.gov (United States)

    Bhattacharyya, Debnath; Robles, Rosslin John; Kim, Tai-Hoon; Bandyopadhyay, Samir Kumar

    In this paper, we propose a method to identify abnormal growth of cells in breast tissue and suggest further pathological test, if necessary. We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps. Normal ductal epithelial cells and ductal / lobular invasive carcinogenic cells also consider for comparison here in this paper. In fact, features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue. We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some greater extent.

  16. Diffusion-weighted imaging and (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer: Correlation of the apparent diffusion coefficient and maximum standardized uptake values with prognostic factors.

    Science.gov (United States)

    Karan, Belgin; Pourbagher, Aysin; Torun, Nese

    2016-06-01

    To evaluate the correlations between the apparent diffusion coefficient (ADC) value and the standardized uptake value (SUV) with prognostic factors in breast cancer. Seventy women with invasive breast cancer (56 cases of invasive ductal carcinoma, four of mixed ductal and lobular invasive carcinoma, three of lobular invasive carcinoma, two of micropapillary carcinoma, and one each of mixed ductal and mucinous carcinoma, mucinous carcinoma, medullary carcinoma, metaplastic carcinoma, and tubular carcinoma) were included in this study. All patients underwent presurgical breast magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) at 1.5T and whole-body (18) F-fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET) / computed tomography (CT). For all invasive breast cancers and invasive ductal carcinomas, we assessed the relationships among ADC, SUV, and pathological prognostic factors. Both the median ADC value and maximum SUV (SUVmax) were significantly associated with vascular invasion (P = 0.008 and P = 0.026, respectively). SUVmax was also significantly correlated with tumor size (P = 0.001), histological grade (P = 0.001), lymph node status (P = 0.0015), estrogen receptor status (P = 0.010), and human epidermal growth factor receptor 2 status (P = 0.020), whereas ADC values were not. The correlation between the ADC and SUVmax was not significant (P = 0.356; R = -0.112). Mucinous carcinoma showed high ADC and relatively low SUVmax. Medullary carcinoma showed low ADC and high SUVmax. When we evaluated the relationships among ADC, SUVmax, and prognostic factors in the 56 invasive ductal carcinomas, our statistical results were not significantly changed, except SUVmax was also significantly associated with progesterone receptor status (P = 0.034), but not lymph node status. SUVmax may be valuable for predicting the prognosis of breast cancer. Both ADC and SUVmax are useful to predict vascular invasion. J. Magn. Reson. Imaging 2016

  17. c-MYC is a radiosensitive locus in human breast cells.

    Science.gov (United States)

    Wade, M A; Sunter, N J; Fordham, S E; Long, A; Masic, D; Russell, L J; Harrison, C J; Rand, V; Elstob, C; Bown, N; Rowe, D; Lowe, C; Cuthbert, G; Bennett, S; Crosier, S; Bacon, C M; Onel, K; Scott, K; Scott, D; Travis, L B; May, F E B; Allan, J M

    2015-09-17

    Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.

  18. Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia

    DEFF Research Database (Denmark)

    Gudjonsson, Thorarinn; Adriance, Melissa C; Sternlicht, Mark D;

    2005-01-01

    The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most...... the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial...... and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia....

  19. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    Science.gov (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  20. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    Science.gov (United States)

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.

  1. Tropomyosin-1, A Putative Tumor-Suppressor and a Biomarker of Human Breast Cancer

    Science.gov (United States)

    2004-10-01

    cDNA. Lobular carcinoma - 2 A polyclonal pan-TM antibody that recognizes multiple TM Phyllodes tumor - 1 Not determined from the initial pathology...AD Award Number: DAMD17-98-1-8162 TITLE: Tropomyosin-1, A Putative Tumor -Suppressor and a Biomarker of Human Breast Cancer PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Tropomyosin-l, A Putative Tumor -Suppressor and a Biomarker DAMD17-98-1-8162 of Human Breast Cancer 6. A UTHOR

  2. Kinase Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0009 TITLE: PRINCIPAL INVESTIGATOR: John Cleveland CONTRACTING ORGANIZATION: H. Lee Moffitt Cancer Center...so designated by other documentation. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer REPORT DOCUMENTATION PAGE Form...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0009 5c

  3. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0008 TITLE: Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer PRINCIPAL INVESTIGATOR...Jan 2017 4. TITLE AND SUBTITLE Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...Investigator [PI], Scripps) and John Cleveland (Collaborating/Partnering PI, Moffitt Cancer Center) seek to validate 40S ribosome assembly as a therapeutic

  4. Cytogenetic report of a male breast cancer

    DEFF Research Database (Denmark)

    Cavalli, L R; Rogatto, S R; Rainho, C A

    1995-01-01

    The cytogenetic findings on G-banding in an infiltrating ductal breast carcinoma in a 69-year-old man are reported. The main abnormalities observed were trisomy of chromosomes 8 and 9 and structural rearrangement in the long arm of chromosome 17 (add(17)(q25)). Our results confirm the trisomy...... of chromosome 8 in the characterization of the subtype of ductal breast carcinomas and demonstrate that chromosome 17, which is frequently involved in female breast cancers, is also responsible for the development or progression of primary breast cancers in males....

  5. Role of COX-2 in the regulation of the metastatic potential of human breast tumor cells

    Directory of Open Access Journals (Sweden)

    M. A. Taipov

    2014-01-01

    Full Text Available The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105, and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

  6. Iron sufficiency in breast-fed infants and the availability of iron from human milk.

    Science.gov (United States)

    McMillan, J A; Landaw, S A; Oski, F A

    1976-11-01

    Four infants were studied who had been exclusively breast-fed for periods varying from 8 to 18 months. All had grown sufficiently to have exhausted their prenatally acquired iron endowment with respect to meeting current needs for maintaining normal hemoglobin levels. All infants had normal hemoglobin values and normal serum iron values. Studies of iron absorption from breast milk and cow's milk were performed in ten normal adults. The absorption of iron from the human milk was significantly higher. These findings suggest that the iron present in human milk is sufficient to meet the iron requirements of the exclusively breast-fed infant until he approximately triples his birthweight.

  7. Dissection of a stem cell hierarchy in the human breast

    DEFF Research Database (Denmark)

    Rubner Fridriksdottir, Agla Jael

    and apoptosis during each menstrual cycle. These changes are most prominent during pregnancy, lactation and involution after breast feeding. These highly dynamic changes are thought to rely on the presence of a breast epithelial stem cell population (reviewed in (Fridriksdottir et al. 2005)). Nevertheless...... al. 2006) is highly warranted as this may lead to identification of those long-term breast resident(s) that accumulate enough genetic hits for clonal expansion and tumor development, i.e. the cellular origin(s) of breast cancer....

  8. Microbial dysbiosis is associated with human breast cancer

    National Research Council Canada - National Science Library

    Xuan, Caiyun; Shamonki, Jaime M; Chung, Alice; Dinome, Maggie L; Chung, Maureen; Sieling, Peter A; Lee, Delphine J

    2014-01-01

    .... In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae...

  9. Antigen binding of human IgG Fabs mediate ERK-associated proliferation of human breast cancer cells.

    Science.gov (United States)

    Wen, Yue-Jin; Mancino, Anne; Pashov, Anastas; Whitehead, Tracy; Stanley, Joseph; Kieber-Emmons, Thomas

    2005-02-01

    Serum-circulating antibody can be linked to poor outcomes in some cancer patients. To investigate the role of human antibodies in regulating tumor cell growth, we constructed a recombinant cDNA expression library of human IgG Fab from a patient with breast cancer. Clones were screened from the library with breast tumor cell lysate. Sequence analysis of the clones showed somatic hypermutations when compared to their closest VH/VL germ-line genes. Initial characterizations focused on five clones. All tested clones displayed stronger binding to antigen derived from primary breast cancers and established breast cancer cell lines than to normal breast tissues. In vitro functional studies showed that four out of five tested clones could stimulate the growth of MDA-MB-231 breast cancer cell lines, and one out of five was able to promote MCF-7 cell growth as well. Involvement of ERK2 pathway was observed. By 1H-NMR spectra and Western blot analysis, it was evident that two tested antibody Fabs are capable of interacting with sialic acid. Our study suggests a possible role for human antibody in promoting tumor cell growth by direct binding of IgG Fab to breast tumor antigen. Such studies prompt speculation regarding the role of serum antibodies in mediating tumor growth as well as their contribution to disease progression.

  10. Simulated lesion, human observer performance comparison between thin-section dedicated breast CT images versus computed thick-section simulated projection images of the breast

    Science.gov (United States)

    Chen, L.; Boone, J. M.; Abbey, C. K.; Hargreaves, J.; Bateni, C.; Lindfors, K. K.; Yang, K.; Nosratieh, A.; Hernandez, A.; Gazi, P.

    2015-04-01

    The objective of this study was to compare the lesion detection performance of human observers between thin-section computed tomography images of the breast, with thick-section (>40 mm) simulated projection images of the breast. Three radiologists and six physicists each executed a two alterative force choice (2AFC) study involving simulated spherical lesions placed mathematically into breast images produced on a prototype dedicated breast CT scanner. The breast image data sets from 88 patients were used to create 352 pairs of image data. Spherical lesions with diameters of 1, 2, 3, 5, and 11 mm were simulated and adaptively positioned into 3D breast CT image data sets; the native thin section (0.33 mm) images were averaged to produce images with different slice thicknesses; average section thicknesses of 0.33, 0.71, 1.5 and 2.9 mm were representative of breast CT; the average 43 mm slice thickness served to simulate simulated projection images of the breast. The percent correct of the human observer’s responses were evaluated in the 2AFC experiments. Radiologists lesion detection performance was significantly (p physicist observer, however trends in performance were similar. Human observers demonstrate significantly better mass-lesion detection performance on thin-section CT images of the breast, compared to thick-section simulated projection images of the breast.

  11. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K

    1996-01-01

    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen recepto...

  12. Human papilloma virus identification in breast cancer patients with previous cervical neoplasia

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2016-01-01

    Full Text Available Purpose: Women with human papilloma virus (HPV associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i identify high risk for cancer HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii determine if these HPVs were biologically active.Methods: A range of polymerase chain reaction (PCR and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. Results: The same high risk HPV types were identified in both the cervical and breast specimens in 13 (46% of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001. Conclusions: These findings indicate that high risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of 2 similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  13. A feasibility study of soft embalmed human breast tissue for preclinical trials of HIFU- preliminary results

    Science.gov (United States)

    Joy, Joyce; Yang, Yang; Purdie, Colin; Eisma, Roos; Melzer, Andreas; Cochran, Sandy; Vinnicombe, Sarah

    2017-03-01

    Breast cancer is the commonest cancer in women in the UK, accounting for 30% of all new cancers in women, with an estimated 49,500 new cases in 20101. With the widespread negative publicity around over-diagnosis and over-treatment of low risk breast cancers, interest in the application of non-invasive treatments such as magnetic resonance imaging (MRI) guided high intensity focused ultrasound (HIFU) has increased. Development has begun of novel US transducers and platforms specifically designed for use with breast lesions, so as to improve the range of breast lesions that can be safely treated. However, before such transducers can be evaluated in patients in clinical trials, there is a need to establish their efficacy. A particular issue is the accuracy of temperature monitoring of FUS with MRI in the breast, since the presence of large amounts of surrounding fat can hinder temperature measurement. An appropriate anatomical model that imposes similar physical constraints to the breast and that responds to FUS in the same way would be extremely advantageous. The aim of this feasibility study is to explore the use of Thiel embalmed cadaveric tissue for these purposes. We report here the early results of laboratory-based experiments sonicating dissected breast samples from a Thiel embalmed soft human cadaver with high body mass index (BMI). A specially developed MRI compatible chamber and sample holder was developed to secure the sample and ensure reproducible sonications at the transducer focus. The efficacy of sonication was first studied with chicken breast and porcine tissue. The experiments were then repeated with the dissected fatty breast tissue samples from the soft-embalmed human cadavers. The sonicated Thiel breast tissue was examined histopathologically, which confirmed the absence of any discrete lesion. To investigate further, fresh chicken breast tissue was embalmed and the embalmed tissue was sonicated with the same parameters. The results confirmed the

  14. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    Science.gov (United States)

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  15. Combined photoacoustic and ultrasound imaging of human breast in vivo in the mammographic geometry

    Science.gov (United States)

    Xie, Zhixing; Lee, Won-Mean; Hooi, Fong Ming; Fowlkes, J. Brian; Pinsky, Renee W.; Mueller, Dean; Wang, Xueding; Carson, Paul L.

    2013-03-01

    This photoacoustic volume imaging (PAVI) system is designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3D ultrasound (AUS). The good penetration of near-infrared (NIR) light and high receiving sensitivity of a broad bandwidth, 572 element, 2D PVDF array at a low center-frequency of 1MHz were utilized with 20 channel simultaneous acquisition. The feasibility of this system in imaging optically absorbing objects in deep breast tissues was assessed first through experiments on ex vivo whole breasts. The blood filled pseudo lesions were imaged at depths up to 49 mm in the specimens. In vivo imaging of human breasts has been conducted. 3D PAVI image stacks of human breasts were coregistered and compared with 3D ultrasound image stacks of the same breasts. Using the designed system, PAVI shows satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides with mild compression in the mammographic geometry. With its unique soft tissue contrast and excellent sensitivity to the tissue hemodynamic properties of fractional blood volume and blood oxygenation, PAVI, as a complement to 3D ultrasound and digital tomosynthesis mammography, might well contribute to detection, diagnosis and prognosis for breast cancer.

  16. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles