Application of Stem Cell Markers in Search for Neoplastic Germ Cells in Dysgenetic Gonads, Extragonadal Tumors, and in Semen of Infertile Men

Summary Germ cell tumours (GCTs) are a complex entity. Current areas of attention include early detection and avoidance of unnecessary over-treatment. Novel findings regarding diagnosis of GCTs located in various anatomical sites are described, particularly testicular GCTs and their common progenitor, carcinoma in situ (CIS). Recognition of CIS enables intervention before tumour development, but nevertheless, testicular GCTs are sporadically diagnosed at the pre-invasive stage where minimal treatment is necessary. As presence of CIS is asymptomatic, a simple screening method is needed when CIS is suspected (i.e. in males investigated for infertility). To develop approaches for early detection CIS gene expression studies have been performed showing many similarities with embryonic stem cells with confirmation of established markers (i.e. PLAP, OCT-3/4, KIT) and identification of novel markers (i.e. AP-2γ, NANOG). We have reported a very promising new approach of AP-2γ (or OCT3/4) based immunocytological semen analysis (specificity 93.6%, sensitivity 54.5%). Comparative studies of gonadal/extragonadal GCTs have revealed resemblance pointing towards similar, but not identical, origins. Moreover, infertility and testicular cancer are connected in the ‘Testicular Dysgenesis Syndrome’ and 25% of contralateral testes from testicular GCT patients harbour dysgenetic features, including impaired spermatogenesis. Thus, recent data have provided potential diagnostic tools including CIS detection in semen, microarray-based tumour classification, additional serological GCT markers, and novel stem cell markers for immunohistochemical diagnosis of gonadal and extragonadal GCTs. Many CIS candidate genes are yet uninvestigated, and information from these could increase knowledge about CIS tumour initiation/progression and be used for optimisation of a non-invasive detection method.