HGF/c-Met is one of the signaling pathways that determine the invasiveness and metastatic potential of various cancers, however, its significance for the progression of endometrial cancer (EC) remains not entirely clear. The aim of this study was to investigate HGF and c-Met expression in tumours of EC patients in relation to the presence of metastasis.
The study was carried out retrospectively on 57 endometrial carcinomas including 32 samples from EC patients with metastasis. Protein expression was evaluated by immunohistochemistry using polyclonal antibody against HGF (PA5-83494, Invitrogene, Sweden) and monoclonal c-Met (EP1454Y, Bio SB, USA) for the percentage of stained cells (labeling index, %). Expression analysis was performed separately in epithelial tumour cells and fibroblasts of the surrounding stroma. Nonparametric Mann-Whitney U-test was used to compare differences between groups.
The mean level of HGF expression in epithelial tumour cells was 18.5 ± 3.3%, in stromal fibroblasts – 14.8 ± 3.6%. The corresponding indices for c-Met were 17.5 ± 3.3 and 18.5 ± 3.8%, respectively. No statistically significant difference was observed in HGF and c-Met expression in epithelial tumour cells in EC patients regarding the presence of metastasis. However, an increased expression of HGF was detected in the stromal fibroblasts of EC patients with metastasis compared to those without metastasis (24.3 ± 6.0 and 2.8 ± 1.3%, respectively, p <0.05). In addition, in patients with metastasis, c-Met expression was higher in stromal fibroblasts of carcinomas that invaded 50% or more of the myometrium in contrast to the cases with less than 50% myometrial invasion (27.8 ± 6.8 and 0.9 ± 0.5%, p <0.05).
Increased expression of HGF and c-Met in stromal fibroblasts of endometrial carcinomas is associated with the presence of metastasis and may be coincide with deep myometrial invasion in EC patients. Obtained results revealed that stromal expression of these proteins might contribute to the aggressiveness of EC.
Legal entity responsible for the study
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Science of Ukraine, Kyiv, Ukraine.
National Academy of Science of Ukraine, Kyiv, Ukraine.
All authors have declared no conflicts of interest.