Background Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type.
Aim In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women.
Methods Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes.
Results Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome.
Conclusion Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC.
- triple negative breast cancers
- basal-like phenotype
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Handling editor Tahir S Pillay.
Contributors The study was designed and directed by PHT and coordinated by JY. JY, AAT, JCTL and MI acquired the data. The analysis was done by AAT and BL; SN and JI provided advice and guidance from breast pathology and clinical perspectives. JY, JCTL and AAT drafted the manuscript, which was commented on and revised by all authors.
Funding This article was funded by the A*STAR Biomedical Research Council, National Medical Research Council Stratified Medicine Programme Office (SMPO201302) awarded to Dr PH Tan. Dr J Iqbal is a recipient of the Transition Award from the Singapore National Medical Research Council (NMRC/TA/0041/2015).
Competing interests None declared.
Ethics approval SingHealth centralised institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.