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

• Published in: Clinical cancer research 2001-09, Vol.7 (9), p.2770-2775
• Main Authors: MORONI, Mauro, VERONESE, Silvio, SCHIAVO, Roberta, CARMINATI, Ornella, SORENSEN, Boe S, GAMBACORTA, Marcello, SIENA, Salvatore
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chorionic Gonadotropin, beta Subunit, Human - analysis; Gene Expression Regulation, Neoplastic; Germinoma - genetics; Germinoma - metabolism; Germinoma - pathology; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Male; Male genital diseases; Medical sciences; Phosphorylation; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Testicular Neoplasms - genetics; Testicular Neoplasms - metabolism; Testicular Neoplasms - pathology; Transforming Growth Factor alpha - analysis; Tumors
• ISSN: 1078-0432; 1557-3265

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-α (TGF-α)] 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 β-human chorionic gonadotropin (β-HCG), EGFR 1, HER-2/ neu , TGF-α, 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 β-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 β-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-α, 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 β-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 β-HCG expression in mixed GCTs.