Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas

OBJECTIVE: The purpose of this study is to evaluate the significance of the c-Met/hepatocyte growth factor receptor expression in invasive cervical carcinoma. METHODS: Ninety-Four patients with FIGO stage 1B disease, treated primarily with surgery, were studied immunohistochemically. Of the cases, 67 were squamous carcinoma and 27 were nonsquamous (10 were adenocarcinoma, 15 were adenosquamous carcinoma, and 2 were indifferentiated carcinoma). Immunohistochemically stained c-Met slides of primary malignancies were evaluated blindly of clinical outcome and other histopathological factors. RESULTS: Overexpression of c-Met was found in 56 of 94 specimens. Primary tumors which show recurrences were found to be c-Met overexpressors. Univariate survival analysis (Kaplan-Meier) showed that c-Met overexpression is significantly correlated with disease-free survival. Moreover the diameter of the primary tumor, deep cervical stromal invasion, presence of metastatic lymph node, number of metastatic lymph nodes and c-Met overexpression were significantly correlated with overall 5-year survival. Furthermore multivariant analysis with Cox regression showed that the presence of metastatic lymph node and immunopositivity for c-Met are significantly correlated with overall survival, while c-Met overexpression was found to be an independent variable for disease-free survival. CONCLUSION: These results reveal that c-Met oncogene overexpression is an important parameter for disease progression, recurrence, and survival in early-stage invasive uterine cervix carcinomas.