Antibodies against Gag and Env proteins encoded by human endogenous retrovirus (HERV)-K genomes are found in the sera of patients with classical seminoma. This prompted us to study ovarian and testicular germ cell tumors, their precursor lesions, dysgenetic gonads, and trophoblast lesions for expression of HERV-K sequences by in situ hybridization using radioactive and non-radioactive probes. Expression of HERV-K sequences was found in all testicular and ovarian germ cell tumors with the exception of teratomas and spermatocytic seminomas. HERV-K expression was also found in testicular intraepithelial neoplasia (so-called carcinoma in situ) as well as in gonocytes of dysgenetic gonads. Among gestational trophoblastic lesions, HERV-K expression was regularly found in choriocarcinomas, but not in non-invasive molar lesions. There was no evidence for HERV-K expression in differentiated embryonal and adult tissues. The findings point to a common molecular pathogenesis of most germ cell tumor entities and malignant gestational trophoblastic disease. They furthermore support the concept of carcinoma in situ as a precursor lesion common to most testicular germ cell tumors. Conceivably, the detection of HERV-K gene products in body fluids and tissues will aid diagnosis and monitoring of germ cell tumors and related lesions.
