Current view on testicular tumors from a developmental biological perspective : Important biomarkers and molecular pathological investigations

Abstract

Germ cell tumors (GCTs) are the most common type of cancer in Germany in young men between 15 and 44years of age. The routinely performed diagnostic procedures are essential for the patient's treatment, but can be difficult due to heterogenous histologies. Additionally, the molecular mechanisms of the development of the special forms growing teratoma syndrome (GTS) and testicular tumors with malignant somatic transformation (MST) as well as of therapy resistance are not fully understood. Updated understanding of the molecular processes underlying GCT development and their special forms as well as recommendations for new and useful biomarkers. The development of GCTs is adynamic process largely influenced by the microenvironment. Seminomas (SEs) in particular seem to posses ahigher cellular plasticity than previously assumed, allowing SEs to be reprogrammed into an embryonal carcinoma (EC) or differentiate into extra-embryonal tissues (yolk sac tumors [YSTs], trophoblastic differentiation). Novel serological (mi371a-3p) and pathological (FOXA2) biomarkers are well suited to early detect GCTs and YSTs, respectively. For more aggressive tumors and special cases (GTS, MST), there are still no reliable diagnostics or specific/tailored therapies available. The ability of SEs to transit into EC or YSTs should be considered during therapy. Future research should focus on deciphering the special forms GTS and MST as well as the early recognition of YSTs, since their development seems to be an escape mechanism to chemotherapy.