DEVELOPMENTAL ARREST OF GERM-CELLS IN THE PATHOGENESIS OF GERM-CELL NEOPLASIA

Clinical observations and epidemiological evidence suggest that import ant aetiopathological events that cause neoplastic transformation of t he male germ cell may occur in fetal life or early infancy. The incide nce of germ cell neoplasia is high in individuals with various disorde rs of gonadal development and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity syndrome. Increased risk has also been noted in individuals with trisomy 21, idiopathic infertility and low birth weight. Infertility is sometimes associated with small aber rations of sex chromosomes (e.g. low frequency mosaicism XY/XO) which can also be found in patients with testicular cancer. The variety of c onditions that predispose to testicular neoplasia and the rise in its incidence in many countries speaks for the influence of environmental factors which may affect genetically predisposed individuals. We hypot hesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differe ntiation arrest which may render them susceptible to neoplastic transf ormation. Morphologically homogenous premalignant carcinoma in situ (C IS) cells have the potential to differentiate into a variety of histol ogical forms of overt testicular tumours. Analysis of cell surface ant igens expressed by CIS cells found in the vicinity of pure and mixed t umours demonstrates that CIS cells are phenotypically heterogeneous. C omparison of the phenotypes of CIS cells, primordial germ cells, human embryonal carcinoma cells and closely related primate embryonal stem cells reveals various similarities but also differences. We speculate that phenotypical heterogeneity of CIS cells may be associated with th eir potential to give rise to different tumour types, and may be relat ed to the developmental stage of the early germ cell which has undergo ne malignant transformation.