title: Role of epithelial-mesenchymal transition markers in triple-negative breast cancer.
abstract: 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.
authors.affiliation: Department of Clinical Pathology, Tuen Mun Hospital, 23 Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong.
authors.forename: Sai Yin
authors.initials: SY
authors.lastname: Cheung
authors.forename: Yvonne Jia Yu
authors.initials: YJ
authors.lastname: Boey
authors.forename: Valerie Cui Yun
authors.initials: VC
authors.lastname: Koh
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.forename: Jeffrey Chun Tatt
authors.initials: JC
authors.lastname: Lim
authors.forename: Jabed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta