Role of epithelial–mesenchymal transition markers in triple-negative breast cancer
- 570 Downloads
Triple-negative breast cancers (TNBCs) are a heterogeneous group of breast tumours that are often associated with adverse pathological characteristics, poorer clinical outcomes and lack of targeted therapeutic options. Epithelial–mesenchymal transition, which plays a crucial role in tumour development and progression, is characterised by a transition from epithelial to mesenchymal phenotype and loss of proteins involved in maintaining cell junctions. We aimed to correlate protein expression of E-cadherin, Snail2 and transforming growth factor beta (TGF-β) with clinicopathological parameters and survivals of a series of patients with TNBC. The study cohort comprised 767 TNBCs diagnosed at the Department of Pathology, Singapore General Hospital from 1994 to 2012. Immunohistochemistry was performed on sections cut from tissue microarrays using the polymeric method. Staining intensity and percentage of positive tumour cells were evaluated and correlated with clinicopathological findings and clinical outcomes. Loss of E-cadherin expression, Snail2 positivity, cytoplasmic and nuclear expression of TGF-β were observed in 265 (35.2 %), 241 (32.0 %), 272 (36.2 %) and 262 (34.8 %) tumours, respectively. Histological grade significantly correlated with Snail2 positivity (P < 0.001) and loss of membranous E-cadherin expression (P = 0.003). Nuclear expression of TGF-β was inversely correlated with histological grade (P = 0.010). Median follow-up was 73 months, with a maximum of 236 months. Despite a graphical curve for earlier recurrence in patients with tumours harbouring a combinational phenotype of loss of membranous E-cadherin and positive Snail2 expression, there was no statistical significance. Similarly for women with tumours expressing cytoplasmic TGF-β, graphical representation showed poorer metastasis-free survival but without statistical significance. Loss of membranous E-cadherin and positive Snail2 expression are significantly associated with high-grade TNBCs. More work is needed to improve understanding of the role of TGF-β in TNBC.
KeywordsEMT TNBC Snail2 E-cadherin TGF-β
This study is part of a research project approved by the SingHealth Centralised Institutional Review Board (CIRB Ref: 2013/664/F) and was funded by the Stratified Medicine Programme Office (Grant No: SMPO201302).
Compliance with Ethical Standards
Conflict of interest
- 6.Iwase H, Kurebayashi J, Tsuda H, Ohta T, Kurosumi M, Miyamoto K, Yamamoto Y, Iwase T (2010) Clinicopathological analyses of triple negative breast cancer using surveillance data from the registration committee of the japanese breast cancer society. Breast Cancer 17:118–124CrossRefPubMedGoogle Scholar
- 18.Members of the Guidelines Working Group of the National Coordinating Committee for Breast Pathology (2005) Pathology reporting of breast disease. NHS Cancer Screening Programmes and The Royal College of Pathologists, United KingdomGoogle Scholar
- 25.Gobbi H, Arteaga CL, Jensen RA, Simpson JF, Dupont WD, Olson SJ, Schuyler PA, Plummer WD, Page DL (2000) Loss of expression of transforming growth factor beta type ii receptor correlates with high tumour grade in human breast in situ and invasive carcinomas. Histopathology 36:168–177CrossRefPubMedGoogle Scholar
- 26.Ding X, Park SI, McCauley LK, Wang CY (2013) Signaling between transforming growth factor β (tgf-β) and transcription factor snai2 represses expression of microrna mir-203 to promote epithelial-mesenchymal transition and tumor metastasis. J Biol Chem 288:10241–10253PubMedCentralCrossRefPubMedGoogle Scholar
- 29.Schwartz AM, Henson DE, Chen D, Rajamarthandan S (2014) Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: a study of 161 708 cases of breast cancer from the seer program. Arch Pathol Lab Med 138:1048–1052CrossRefPubMedGoogle Scholar