The expression of hepatocyte growth factor (HGF) and c-Met in uterine serous carcinoma

ObjectiveThe hepatocyte growth factor (HGF) receptor c-Met plays an important role in tumor dissemination by activating mitogenic signaling pathways. The goal of this study was to investigate immunohistochemical (IHC) staining patterns of HGF and c-Met in endometrioid endometrial cancer (EC) and uterine serous cancer (USC) and to correlate staining with patient outcomes.MethodsA tissue microarray was created using tissue from patients with atrophic endometrium (AE), grade 1 EC, grade 3 EC, and USC. Immunohistochemistry was used to detect c-Met, phosphorylated c-Met (p-c-Met), and HGF expression. Differences between IHC staining intensity were calculated using t-tests. Correlations between staining and clinicopathologic variables were determined by Chi-square testing for categorical variables and t-tests for continuous variables. Kaplan-Meier curves were constructed to analyze survival in USC.ResultsPatients with cancer had more total c-Met and HGF expression than those with AE (p = 0.037, p < 0.001 respectively), but no difference in p-c-Met staining. Total c-Met and HGF staining was significantly different between groups (p = 0.042, p < 0.001 respectively). This difference was accounted for by greater c-MET expression in USC compared to AE (p = 0.027). Depth of invasion, stage, and lymph node status were not significantly related to staining intensity. Patients with strong c-Met and HGF staining had decreased overall survival compared to patients with weaker staining.ConclusionsHGF and c-Met may play a role in the progression of endometrial cancer and should be studied further as prognostic and therapeutic tools.

Research Highlights►c-Met and HGF are overexpressed in endometrial cancer ►Overexpression is higher in patients with serous cancer that low grade carcinoma ►In uterine serous carcinoma increased expression correlates to decreased survival