Expression of the RNA component of human telomerase in adult testicular germ cell neoplasia

BACKGROUND, During human development, telomerase is repressed in most somat ic cells, whereas it is maintained in male germline cells. Reactivation of telomerase has been associated with somatic cancers. To the authors' knowle dge, the role of telomerase in germ cell derived malignancies has not previ ously been evaluated. METHODS. A radioactive in situ hybridization method was used to study the e xpression of the RNA component of human telomerase (hTR) in 22 cases of adu lt testicular germ cell neoplasia encompassing all major histomorphologic t ypes. For precise cell identification, hTR in situ hybridization was combin ed with immunohistochemistry in select cases. RESULTS. Testicular germ cell tumors showed differential expression of hTR. The highest level of expression was seen in embryonal carcinoma. Seminoma and unclassified intratubular germ cell neoplasia exhibited moderate levels of expression. Yolk sac tumor was characterized by a range of expression, which mirrored its morphologic variation. Immature teratoma recapitulated t he down-regulation of telomerase manifested during human embryogenesis. Mat ure teratoma represented the adult pattern of somatic repression. Notably, choriocarcinoma showed modest expression. The expression of spermatocytic s eminoma was intermediate between that of classic seminoma and embryonal car cinoma. No difference in expression was evident between matching intratubul ar and invasive components. In nonneoplastic testis, hTR expression was dow n-regulated during spermatogenesis and was absent in spermatozoa. Expressio n was negligible in rete testis and interstitial Leydig cells, and low in e pididymis. Unexpectedly, Sertoli cells, which are testicular accessory soma tic cells, displayed the most intense expression observed in this study. CONCLUSIONS. In testicular germ cell tumors of young adults (and during spe rmatogenesis), hTR expression is down-regulated with differentiation, irres pective of the aggressiveness of the tumors. Spermatocytic seminoma, regard ed as a low grade malignancy, shows moderately intense expression. (C) 1999 American Cancer Society.