Retrospective assessment of TCF12 expression in early invasive breast cancer and ovarian cancer: prognostic implications and biological insights

Transcription factor 12 (TCF12) is a basic helix-loop-helix transcription factor implicated in tissue differentiation and pathogenesis in many types of cancer. Its role in breast and ovarian cancer remains poorly understood. TCF12 protein expression was assessed by immunohistochemistry in 1,514 primary breast tumours and 423 ovarian tumours. TCF12 mRNA expression was analysed in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n=1,980). Associations between protein expression with clinicopathological variables and patient survival were evaluated. In breast cancer, TCF12 was predominantly expressed in the nucleus with low nuclear expression observed in 32% of cases. Both TCF12 protein and mRNA expression were significantly associated with adverse clinicopathological features, including larger tumour size, higher Nottingham Prognostic Index category, and oestrogen receptor-negative tumours. Low nuclear TCF12 expression was associated with adverse breast cancer-specific survival, particularly in oestrogen receptor-positive tumours; it remained an independent adverse prognostic factor in the multivariate analysis. Similar findings were observed when assessing TCF12 mRNA. No association was observed between TCF12 expression and survival of ovarian cancer patients. Low TCF12 expression identified a biologically aggressive subset of breast cancers with poor prognosis. These findings highlight the potential of TCF12 as a prognostic biomarker in breast cancer. No association between TCF12 expression and survival was observed in ovarian cancer patients, suggesting tumour-specific roles.