c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma

Aims: Receptor-type tyrosine kinases are important in cell signal transduct ion and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c-met is a tyrosine kinase receptor and its li gand is hepatocyte growth factor (HGF). In this study, we have evaluated c- met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and pa tients' survival. We also studied for the first time c-met expression in as sociation with E-cadherin and beta-catenin expression. Methods and results: Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and beta-catenin. c-met immunoreactivit y was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c-erbB-2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c-met immunor eactivity did not correlate with lymph node status, tumour size and stage o f the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c-met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c-met staining was compare d with E-cadherin and beta-catenin expression, a statistical significant co rrelation was established between c-met immunoreactivity and abnormal beta- catenin expression (P = 0.025) suggesting possible involvement of c-met in the downregulation of the E-cadherin-catenin complex, possibly through tyro sine phosphorylation of beta-catenin. Conclusion: c-met immunohistochemical expression seems to be associated wit h abnormal beta-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.