Endocrine Abstracts

Various types of human germ cell tumors (GCTs) can be found, referred to as type I, II and III. The type I are the teratomas and yolk sac tumors of neonates and infants. No genomic aberrations have been identified in teratomas, while yolk sac tumors show chromosomal imbalances related to chromosomes 1, 6 and 20. Type II GCTs are the seminomas and nonseminomas, derived from carcinoma in situ (CIS)/intratubular germ cell neoplasia unclassified (ITGCNU). CIS/ITGCNU and seminoma cells mimic primordial germ cells/gonocytes, amongst others characterized by expression of the diagnostic marker OCT3/4-POU5F1. All invasive tumors show gain of the short arm of chromosome 12. The type III GCTs, i.e. spermatocytic seminomas, occur predominantly in elderly, and only in the testis. They originate from primary spermatocytes, and show consistent gain of chromosome 9, of which DMRT1 is a candidate. GCTs show specific patterns of mRNA and microRNA expression, of possible diagnostic and prognostic value. Besides familial predisposition and infertility, disorders of sex differentiation (DSD) is a risk factor for type II GCTs. This specifically forms of hypovirilization and gonadal dysgenesis, in the presence of part of the GBY region. Besides CIS/ITGCNU, gonadoblastoma can be the precursor in DSD patients. Gonadoblastoma is the earliest developmental stage in the genesis of GCTs. TSPY (testis specific protein on the Y chromosome) is a likely candidate to explain the requirement of the GBY region for malignant transformation of germ cells. A significant limiting diagnostic factor in DSD is lack of specific markers for CIS/ITGCNU in case of maturation delay of germ cells. The type II GCTs are in fact an embryonic cancer in adult patients. This explains a number of specific characteristics, like their histology (totipotency), overall sensitivity to DNA-damaging agents, as well as their chromosomal and genetic constitution.