CTEN (C-terminal tensin-like), a novel oncogene overexpressed in invasive breast carcinoma of poor prognosis

C-terminal tensin-like (CTEN) gene is a member of the TENSIN gene family, involved in cell migration and localised at focal adhesion sites. This study was designed to explore the prevalence and clinical significance of CTEN expression in a large and well-characterised series (n = 1,409) invasive breast cancer (BC) cases with long term follow-up (median 11 years), using immuno-histochemistry and tissue microarray. Moderate to strong cytoplasmic immunoreactivity for CTEN was observed in 90% of the studied cases. CTEN expression was significantly associated with poor prognostic variables including larger tumour size (P = 0.044), higher histological grade (P = 0.019), axillary nodal involvement (P = 0.035) and poor Nottingham Prognostic Index (P = 0.016). Significant associations were observed between increased CTEN expression and up-regulation of phosphorylated-Akt (P-Akt), PIK3 and N-cadherin proteins (P\0.001). Kaplan-Meier survival analysis demonstrated that patients with high CTEN expression had significantly shorter Breast Cancer Specific Survival (P = 0.004) and Metastasis-Free Survival (P = 0.041) than those with low-CTEN expression. Multivariate analysis showed that CTEN was not an independent prognostic marker in BC. In conclusion, our results demonstrated the oncogenetic role of increased CTEN expression and its association with poor prognostic parameters. These data could help in prognostic assessment in BC patients.