Advances in basic research on testicular germ cell tumors. Clinical implications

Human testicular germ cell tumors (GCTs) comprise several types of neoplasias with different pathogenesis and clinical behavior, referred to as types I, II, and III. They represent different cells of origin, explaining their specific characteristics, including expression of markers useful for diagnosis. Here, the most frequent variant of testicular GCTs will be discussed, i.e., the type II GCT, referred to as TGCTs, i.e. seminomas and nonseminomas. Various risk factors have been identified. These tumors originate from a transformed primordial germ cell/gonocyte, known as carcinoma in situ (CIS), that is able to generate all differentiation lineages (omnipotent). The c-KIT-stem cell factor pathway is of relevance for development of this cancer. Retention of embryonic characteristics probably explains the unique treatment responsiveness to DNA-damaging agents. OCT3/4, a marker of pluripotency, is the optimal diagnostic marker for seminoma and embryonal carcinoma, and CIS, the latter also in semen, suitable for non-invasive screening. In addition, distinction between seminoma and embryonal carcinoma can be made using SOX17 and SOX2. Micro-satellite instability as well as BRAF mutations have been identified to be related to treatment resistance, possibly leading to improved clinical management