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.

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.

Diagnosis of Papillary Breast Lesions on Core Needle Biopsy: Upgrade Rates and Interobserver Variability

2019 ◽  
Vol 27 (7) ◽  
pp. 736-743 ◽  
Author(s):  
Lianqun Qiu ◽  
Daniel D. Mais ◽  
Marlo Nicolas ◽  
Jennifer Nanyes ◽  
Kenneth Kist ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Breast Imaging ◽  
Interobserver Variability ◽  
Ductal Carcinoma ◽  
Atypical Ductal Hyperplasia ◽  
Breast Lesions ◽  
Ductal Hyperplasia ◽  
Papillary Lesions

The histologic distinction between papillary breast lesions remains challenging, especially with core biopsy (CB) specimens. A retrospective review of the clinical, imaging, and histologic findings was performed for patients with papillary breast lesions on CB from 2013 to 2017. The interpretation accuracy was expressed as upgrade rate relative to the excision diagnosis. Diagnostic reproducibility with and without immunohistochemistry was analyzed as interobserver variability among 3 board-certified pathologists. Among 57 papillary lesions with biopsies and excisions available for review, the upgrade rates were 0% for benign papilloma, 30% for papilloma with atypical ductal hyperplasia, and 25% for papilloma with ductal carcinoma in situ, resulting in an overall upgrade rate of 11.1%. There were no statistical differences between patients in an upgrade group and others, when comparing the patient age, clinical presentation, BI-RADS (Breast Imaging Reporting and Database System) category, location, and histologic grade. The overall interobserver variability of the 60 consecutive core biopsies of papillary breast lesions by morphology alone was in the “substantial” agreement range (κ = 0.79, 86% agreement), with an excellent κ score of 0.88 for papilloma (92% agreement). “Substantial” and “fair” κ values were seen for papilloma with atypical ductal hyperplasia/ductal carcinoma in situ (0.74, 84% agreement) and invasive carcinoma (0.40, 60% agreement). Use of immunohistochemical stains improved the κ values into “excellent” range (0.92, 94% agreement). Our study favors a conservative approach in the management of benign papillomas, at least in cases of good radiologic-pathologic concordance. Papillary breast lesions with atypia/malignancy show lower diagnostic reproducibility on CB, and utility of immunohistochemistry is recommended in challenging cases.

Papillary Breast Lesions: Association with Malignancy and Upgrade Rates on Surgical Excision

2017 ◽  
Vol 83 (11) ◽  
pp. 1294-1297 ◽  
Author(s):  
Hanh-tam Tran ◽  
Asma Mursleen ◽  
Sahar Mirpour ◽  
Omar Ghanem ◽  
Maen J. Farha
Keyword(s):  
Carcinoma In Situ ◽  
Breast Lesion ◽  
Ductal Carcinoma ◽  
Surgical Excision ◽  
Intraductal Papilloma ◽  
Breast Lesions ◽  
Aggressive Approach ◽  
Papillary Lesions ◽  
Benign Papilloma

Intraductal papilloma falls under the category of benign breast mass. However, recent studies show that it can harbor occult carcinoma. The management of benign intraductal papilloma remains controversial because of its nonspecific radiologic and histological findings, as well as its association with surrounding malignant pathology. The purpose of this study is to investigate upgrade rates of a benign intraductal papilloma on surgical excision and the need for surgical excision of papillary lesions diagnosed at core needle biopsy. A retrospective review of a single institution's pathology database between 2011 and 2015 identified 43 core biopsies with benign papilloma. We followed the upgrade rates of these lesions on surgical excision. There were 90 biopsies with the diagnosis of benign intraductal papilloma. The average age was 55.2 (range from 24–87 years old). Forty-three had benign intraductal papilloma; 28 of the 43 core biopsies had surgical excision. Two (7.1%) had an upgrade from benign intraductal papilloma to intraductal papilloma with atypia. One (3.6%) had an upgrade to ductal carcinoma in situ. None had invasive cancer. Surgical findings were in agreement with core biopsies in 25 (89.3%) of 28 cases (κ = 0.80, P < 0.0001). Core biopsies have a statistically significant correlation with pathologies on surgical excision in detecting atypia in breast lesion as demonstrated by κ = 0.80. However, the study shows benign intraductal papillomas on core biopsy have an upgrade rate of 10.7 per cent after undergoing surgical excision. As such, we recommend a more aggressive approach including surgical excision of all benign intraductal papillary lesions.

scholarly journals TGF-β1 stimulates epithelial–mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wang ◽  
Cong Xu ◽  
Xia Liu ◽  
Yang Yang ◽  
Lu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Emt Markers ◽  
Tgf Β1

Abstract Background The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer. Methods EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell–cell interactions in the development of invasive breast cancer. Results We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo. Conclusions In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.

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