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Epidermal Growth Factor Receptor Expression and Activation in Nonseminomatous Germ Cell Tumors¹

The Falck Division of Medical Oncology, Departments of Oncology and Hematology [M. M., R. S., O. C., S. S.] and Pathology [S. V., M. G.], Ospedale Niguarda Ca’ Granda, I-20162 Milan, Italy, and Department of Clinical Biochemistry, KH Aarhus University Hospital, Aarhus C, 8000 Denmark [B. S. S.]

Purpose: The goal of this work was to study the expression of epidermal growth factor receptor (by use of monoclonal antibody EGFR 1) and HER-2/neu (by use of monoclonal antibody EGFR 2), as well as EGFR activation [phosphorylated EGFR (P-EGFR)] and autocrine stimulation [ligand transforming growth factor- (TGF-)] markers in a series of 24 testicular tumors [18 nonseminomatous germ cell tumors (GCTs), 1 Leydig cell tumor, and 5 seminomatous GCTs].

Experimental Design: Paraffin-embedded sections of tumors were studied immunohistochemically for ß-human chorionic gonadotropin (ß-HCG), EGFR 1, HER-2/neu, TGF-, and P-EGFR expression. In one case of pure choriocarcinoma, fresh-frozen tumor sections were also evaluated. The presence of EGFR mRNA was studied in the Jar choriocarcinoma cell line using reverse transcription-PCR.

Results: Staining for cell membrane EGFR was detected immunohistochemically in the 16 ß-HCG-positive components of 18 nonseminomatous GCTs as well as in the control Jar choriocarcinoma cell line and normal placenta. In contrast, 1 Leydig cell tumor, 5 seminomatous GCTs, and ß-HCG-negative components of 18 GCTs, as well as control B and T lymphoma cell lines, did not express EGFR. Expression of HER-2/neu, TGF-, and P-EGFR was detected in 25, 36, and 27% of EGFR-positive, nonseminomatous GCTs, respectively. 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 ß-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 negative prognostic significance of ß-HCG expression in mixed GCTs.

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