EXPRESSION OF HEPATOCYTE GROWTH FACTOR AND C-MET RECEPTOR IN STROMAL FIBROBLASTS AND TUMOR CELLS OF ENDOMETRIAL CARCINOMA.

Background: HGF/c-Met is one of the main signaling pathways that ensure communication between epithelial cells and components of the tumor microenvironment determining the invasive and metastatic potential of many cancers. However, the significance of HGF and c-Met in endometrial carcinoma (ECa) progression remains unclear.

Aim: To evaluate copy number variations as well as expression of the c-Met receptor and its ligand HGF in endometrial carcinomas considering the clinical and morphological characteristics of ECa.

Materials and methods: The study was conducted on ECa samples of 57 patients, among which 32 had lymph nodes and/or distant metastasis. The copy number of c-MET gene was estimated by qPCR. The expression of HGF and c-Met in tissue samples was determined by the immunohistochemical method.

Results: Amplification of c-MET gene was detected in 10.5% of the ECa cases. In most carcinomas, a combined expression pattern of HGF and c-Met was established, in which co-expression of these markers was observed in tumor cells, and the content of HGF+ fibroblasts increased in the stroma. The expression of HGF in tumor cells was associated with the tumor differentiation grade and was higher in G3 ECa (p = 0.041). The number of HGF+ fibroblasts in the stromal component increased in the ECa cases with metastasis compared to the cases without metastasis (p = 0.032). The content of stromal c-Met+ fibroblasts was higher in deeply invasive carcinomas of patients with metastases than in tumors with invasion of < 1/2 myometrium (p = 0.035).

Conclusion: Increased expression of HGF and c-Met in stromal fibroblasts of endometrial carcinomas is associated with metastasis in patients with ECa and deep invasion of the tumor into the myometrium, and can contribute to the aggressive course of the disease.