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

نویسندگان

  • M Moroni
  • S Veronese
  • R Schiavo
  • O Carminati
  • B S Sorensen
  • M Gambacorta
  • S Siena
چکیده

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-alpha (TGF-alpha)] 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 beta-human chorionic gonadotropin (beta-HCG), EGFR 1, HER-2/neu, TGF-alpha, 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 beta-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 beta-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-alpha, 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 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 negative prognostic significance of beta-HCG expression in mixed GCTs.

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عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 7 9  شماره 

صفحات  -

تاریخ انتشار 2001