Telomerase activity in germ cell cancers and mature teratomas

Background: An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in hu man tumor cell lines. Male germ cell tumors represent an attractive clinica l model to assess this relationship further because high telomerase activit y is present in normal germ cell progenitors and in embryonal carcinomas th at can differentiate into mature teratomas, To investigate how telomerase a ctivity and the differentiation state of germ cell tumors are related, telo merase activities and telomere lengths were measured in benign testicular t issues, germ cell cancers, and mature or immature teratomas, Methods: By us e of a modified telomeric repeat amplification protocol (TRAP) assay, telom erase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature ter atoma, Telomere lengths were measured in all specimens by restriction diges tion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with tw o-sided Fisher's exact tests. Results: Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimen s. In marked contrast, telomerase activity was not detected in any mature t eratoma (P<.0001), Very long telomeres were detected in some mature teratom as, consistent with telomerase repression as a late event in teratoma forma tion. The immature teratoma, with malignant transformation, had high telome rase activity. Conclusion: Telomerase is active in germ cell cancers and re pressed in mature teratomas, The absence of telomerase activity may contrib ute to the limited proliferative capacity of mature teratomas, These findin gs support the existence of an inverse relationship between telomerase acti vity and the differentiation state of clinical germ cell tumors.