scholarly journals Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lina Ding ◽  
Ying Su ◽  
Anne Fassl ◽  
Kunihiko Hinohara ◽  
Xintao Qiu ◽  
...  
Keyword(s):  
Germline Mutation ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Normal Mammary Gland ◽  
Mutation Carriers ◽  
Breast Tissues

Abstract Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression.

Thymidylate Synthase, a New Myoepithelial Biomarker for Breast Lesions

2019 ◽  
Vol 27 (8) ◽  
pp. 852-858
Author(s):  
Rui Guo ◽  
Yi Tian ◽  
Xueyuan Jin ◽  
Xiaozhong Huang ◽  
Jun Yang
Keyword(s):  
Differential Diagnosis ◽  
Thymidylate Synthase ◽  
Stromal Cells ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Breast Lesions ◽  
Breast Tissues

Background. The identification of myoepithelial cells (MECs) can facilitate the differential diagnosis of breast lesions. We previously found thymidylate synthase (TS) expression in the nuclei of MECs in breast tissues, which prompted us to investigate the usefulness of TS as a sensitive and specific biomarker in the differential diagnosis of breast lesions, similar to other MEC biomarkers (ie, tumor protein [P63] and cluster of differentiation 10 [CD10]). Methods. Immunohistochemistry for TS, P63, and CD10 was performed on paraffin sections from 189 breast specimens. Results. The results showed the intensity of the immunoreactive TS signal to be comparable with that of P63 in the nuclei of MECs. Furthermore, the nuclei of MECs stained strongly for TS and P63 in normal breast tissues (obtained adjacent to invasive breast lesions), benign breast lesions, and carcinoma in situ, whereas the cytoplasm of MECs stained strongly for CD10. The immunoreactive TS signal in the cytoplasm of MECs was variable in 22 out of 32 (65.6%) cases of invasive breast carcinoma and 4 out of 20 cases (20.0%) of ductal carcinoma in situ. We found no immunoreactive TS signal in the nuclei of luminal and stromal cells in breast lesions, although there was a weak positive signal in the cytoplasm of luminal and stromal cells. Conclusions. TS is a sensitive and specific MEC biomarker in the differential diagnosis of breast lesions.

Ductal Carcinoma In Situ in BRCA Mutation Carriers

2007 ◽  
Vol 25 (6) ◽  
pp. 642-647 ◽  
Author(s):  
E. Shelley Hwang ◽  
Jane L. McLennan ◽  
Dan H. Moore ◽  
Beth B. Crawford ◽  
Laura J. Esserman ◽  
...  
Keyword(s):  
High Risk ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Prediction Models ◽  
Ductal Carcinoma ◽  
Brca Mutation ◽  
Univariate Analysis ◽  
Invasive Cancer ◽  
Mutation Carriers

Purpose The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative. Methods We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups. Results Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02). Conclusion DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO.

scholarly journals HIF-1α Overexpression in Ductal Carcinoma In Situ of the Breast in BRCA1 and BRCA2 Mutation Carriers

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56055 ◽  
Author(s):  
Petra van der Groep ◽  
Paul J. van Diest ◽  
Yvonne H. C. M. Smolders ◽  
Margreet G. E. M. Ausems ◽  
Rob B. van der Luijt ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers
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