Overexpression of c-Met hepatocyte growth factor receptors in human prostatic adenocarcinoma

Hepatocyte growth factor (HGF) and c-met proto-oncogene product (c-Met) hav e varied biological functions in different tissues and have been implicated in mitogenic, motogenic and morphogenic responses in both organ regenerati on and carcinogenesis. Some studies have suggested that the overexpression of c-Met and epidermal growth factor receptor (EGFR) are associated with growth advantage, while t ransforming growth factor-beta receptor II (TGF beta R II) is associated wi th growth disadvantage of human prostatic adenocarcinoma. However, it is un clear if the expression of c-Met correlates with the expression of EGFR and TGF beta R II, and with the proliferative status of human prostatic adenoc arcinoma. Using immunohistochemical staining with anti-c-Met (C-l2), anti-E GFR (NCL-EGFR) and anti-TGF beta R II (L-21) antibodies, we determined the frequency of expression of c-MET, EGFR, and TGF beta R II respectively in a series of 134 radical prostatectomy specimens. We evaluated the relationsh ip between the expression of these receptors and clinicopathological charac teristics. Overall, Met immunostaining was detected in 54 of 134 (40.3%) ca ses, EGFR in 45 (33.6%) and TGF beta R II in 64 (48.4%). The overexpression of c-Met was significantly more common in poorly differentiated (P < 0.000 1) and in the diffusely infiltrated specimens (P < 0.0005). In contrast, TG F beta R II was significantly overexpressed in the well differentiated spec imens (P < 0.0001) and associated negatively with c-Met (P < 0.0001). Overa ll, these data suggest that c-Met/HGF receptor and TGF beta R II overexpres sion may be involved in the differentiation of human prostatic adenocarcino ma, c-Met with de-differentiation and TGF beta R II with differentiation.