[Gene products of human endogenous retrovirus (HERV)-K in germ cell and trophoblastic tumors]. / Genprodukte Humaner Endogener Retroviren (HERV)-K in Keimzell- und Trophoblasttumoren.

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.

Expression of human endogenous retrovirus K elements in germ cell and trophoblastic tumors.

Antibodies against proteins encoded by human endogenous retrovirus (HERV)-K family genes are consistently found in the sera of patients with classical seminoma. Furthermore, HERV-K Gag-encoded protein could be detected in corresponding tumor biopsies. Addressing questions as to the extent of HERV gene expression in biologically related lesions, we studied various testicular and ovarian germ cell tumors (GCTs), GCT precursor lesions, and gestational trophoblastic disease (GTD) for the presence of HERV-K gene transcripts in tissue sections. By in situ hybridization using four non-overlapping, isotopically labeled RNA probes specific for HERV-K gag and env sequences on archival tissue samples, consistent HERV-K expression of gag and env genes was found to be common to all GCTs and their testicular precursor lesions with the exception of teratomas, mature and immature, and spermatocytic seminomas. HERV-K expression was also found in malignant GTD (choriocarcinoma) but not in benign GTD (noninvasive molar pregnancy). There was no evidence for HERV-K expression in differentiated embryonal and adult tissues as well as a total of 53 tumors other than GCT or GTD. The findings point to a common molecular pathoetiology of GCT and malignant GTD, have implications for the classification of GCTs, and support the concept of carcinoma in situ as a precursor lesion common to all forms of testicular GCT.

Human papillomavirus type 18 DNA in gestational trophoblastic tissues and choriocarcinomas.

The objectives of our study were to better understand carcinogenesis of gestational trophoblastic tumors and to investigate the possible presence of human papillomavirus types 16 and 18 DNA sequences in these tumors. Amplification-based DNA methodology was used on 11 hydatidiform moles, 5 invasive moles, 8 choriocarcinomas and 9 normal early placental tissues. Human papillomavirus type 16 DNA was not found in any of these tissues. Although human papillomavirus type 18 DNA was also not found in the 9 normal placentas and 5 invasive moles, it was present in 2 of the 11 (18%) hydatidiform moles and in 4 of the 8 (50%) choriocarcinomas.