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

Citation
M. Moroni et al., Epidermal growth factor receptor expression and activation in nonseminomatous germ cell tumors, CLIN CANC R, 7(9), 2001, pp. 2770-2775
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2770 - 2775
Database
ISI
SICI code
1078-0432(200109)7:9<2770:EGFREA>2.0.ZU;2-V
Abstract
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.