Epidermal growth factor receptor expression and activation in nonseminomatous germ cell tumors

Purpose: The goal of this work was to study the expression of epidermal gro wth factor receptor (by use of monoclonal antibody EGFR 1) and HER-2/neu (b y use of monoclonal antibody EGFR 2), as well as EGFR activation [phosphory lated EGFR (P-EGFR)] and autocrine stimulation [ligand transforming growth factor-alpha (TGF-alpha)] markers in a series of 24 testicular tumors [18 n onseminomatous germ cell tumors (GCTs), 1 Leydig cell tumor, and 5 seminoma tous GCTs]. Experimental Design: Paraffin-embedded sections of tumors were studied inum mohistochemically for beta -human chorionic gonadotropin (beta -HCG), EGFR 1, HER-2/neu, TGF-alpha, and P-EGFR expression. In one case of pure chorioc arcinoma, fresh-frozen tumor sections were also evaluated. The presence of EGFR mRNA was studied in the Jar choriocarcinoma cell line using reverse tr anscription-PCR. Results: Staining for cell membrane EGFR was detected immunohistochemically in the 16 beta -HCG-positive components of 18 nonseminomatous GCTs as well as in the control Jar choriocarcinoma cell line and normal placenta. In co ntrast, 1 Leydig cell tumor, 5 seminomatous GCTs, and beta -HCG-negative co mponents of 18 GCTs, as well as control B and T lymphoma cell lines, did no t express EGFR. Expression of HER-2/neu, TGF-alpha, and beta -EGFR was dete cted in 25, 36, and 27% of EGFR-positive, nonseminomatous GCTs, respectivel y. EGFR mRNA was detected in the Jar choriocarcinoma cells. Conclusions: We report data, for the first time, that document EGFR and HER -2/neu expression and indicate EGFR activation and autocrine stimulation in beta -HCG-positive, nonseminomatous GCTs. These findings may be clinically relevant in relation to the recent availability of active EGFR- and HER-2/ neu-targeted pharmaceutical agents and to the extensively described negativ e prognostic significance of beta -HCG expression in mixed GCTs.