Protein overexpression and gene amplification of epidermal growth factor receptor in adult testicular germ cell tumors: potential role in tumor progression.

Little is known about the pathologic significance of epidermal growth factor receptor (EGFR) expression in malignant testicular germ cell tumors (TGCTs) in adults. From the primary tumor sites of a cohort of 110 TGCT cases, we obtained 209 histologically distinct components: 53 intratubular germ cell neoplasia unclassified (IGCNU) lesions, 83 seminomas (66 pure-form seminomas and 17 seminoma components in the mixed-form with nonseminomatous TGCTs), 27 embryonal carcinomas, eight choriocarcinomas, 18 yolk sac tumors, and 20 immature teratomas. Samples were analyzed for expression of EGFR protein and EGFR gene amplification by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. Overexpression of the EGFR protein was detected in 28% of seminomas (27% in the pure-form and 29% in the mixed-form), 11% of embryonal carcinomas, 88% of choriocarcinomas, 44% of yolk sac tumors, and none of the IGCNU lesions or immature teratomas. A higher copy number (≥4 copies per cell) and amplification of the EGFR gene were detected in 20% and 10% of seminomas, 13% and 0% of embryonal carcinomas, 71% and 60% of choriocarcinomas, 15% and 8% of yolk sac tumors, and none of the IGCNU lesions or immature teratomas, respectively. Both higher copy number and amplification of the EGFR gene were positively correlated with immunohistochemical overexpression of EGFR protein (each P < 0.0001). These results suggest that overexpression of EGFR protein and increased copy number or amplification of the EGFR gene occur relatively frequently in primary TGCTs, and may play roles in the formation of invasive cancer and in the progression, especially morphological evolution, of tumors.