New insights into the pathology and molecular biology of human germ cell tumors.

The group of human germ cell tumors (GCTs) is heterogeneous, and comprises neoplasms found at different anatomical locations. They are of interest not only for aspects of their tumor biology, but also from the point of view of developmental biology. GCTs show significant similarities to early germ cell development, most likely related to their cell of origin. Comparative analysis of the tumors and representative normal counterparts can therefore help to define events which are related to the pathogenesis of this cancer. Within the testis, three separate GCT entities have been identified, characterized by differing patho-biological, molecular/cytogenetic, and clinical observations, which will be described in more detail in this review. This article will highlight the most important contributions to the field in the last years. This includes the diagnostic value of OCT3/4, a transcription factor and marker for pluripotency. Furthermore, the invasive GCTs of young adults consistently show a gain of 12p-sequences, of which the exact role, including the gene(s) involved, remains to be elucidated, although interesting candidates have been identified. Finally, treatment sensitivity/resistance of GCTs most likely reflect the intrinsic characteristics of the cells of origin and their derivatives. The pluripotency of GCTs, in particular the possible loss of the embryonic characteristics and acquisition of somatic differentiation, could be a crucial phenomenon in this process.