Human endogenous retrovirus (HERV)-K transcripts in gonadoblastomas and gonadoblastoma-derived germ cell tumours

Gonadoblastomas are rare rumours of abnormal or dysgenetic gonads, often tr ansforming to invasive seminomatous and nonseminomatous germ cell tumours ( GCT), Because of the intimate association of noninvasive and invasive lesio ns, gonadoblastoma may provide clues as to the molecular pathogenesis of GC T, We studied the expression of the human endogenous retrovirus (HERV)-K ga g gene in eight gonadoblastomas arising in phenotypically female patients, including two newborn girls. We also studied testicular biopsies with immat ure Sertoli cell nodules harbouring neoplastic germ cells, a lesion with mo rphological resemblance to gonadoblastoma. In five gonadoblastomas, invasiv e seminoma/dysgerminoma was noted, in two cases with formation of additiona l GCT components. HERV-K gag transcripts were found with moderate levels in gonocytes of all gonadoblastomas and in neoplastic germ cells in testicula r Sertoli cell nodules. All invasive GCT except for teratomas displayed HER V-K transcripts, Thus, expression of HERV-K is induced during fetal or embr yonal development and precedes invasive GCT formation. Although the specifi c role of HERV-K expression remains unknown, the findings place HERV-K expr ession in an appropriate time frame for it to have a role in the molecular pathogenesis of GCT and suggest a precursor-invasive tumour relationship fo r ovarian GCT equivalent to the more common carcinoma in situ of the testis and testicular GCT.