dysgenetic gonadal malignant transformation
Monday 16 May 2011
Gonadoblastoma (GB) is an in situ tumor consisting of a heterogeneous population of mature and immature germ cells, other cells resembling immature Sertoli/granulosa cells, and Leydig/lutein-like cells, may also be present.
Gonadoblastoma almost exclusively affects a subset of patients with intersex disorders and in 30% of them overgrowth of the germinal component of the tumor is observed and the lesion is term dysgerminoma/seminoma.
Several pathways have been proposed to explain the malignant process, and abnormal OCT3/4 expression is the most robust risk factor for malignant transformation.
Some authors have suggested that OCT3/4 and beta-catenin might both be involved in the same oncogenic pathway, as both genes are master regulators of cell differentiation and, overexpression of either gene may result in cancer development.
The mechanism by which beta-catenin participates in GB transformation is not completely clear and exploration of the E-cadherin pathway did not conclusively show that this pathway participated in the molecular pathogenesis of GB.
The proliferation of immature germ cells in GB may be due to an interaction between OCT3/4 and accumulated beta-catenin in the nuclei of the immature germ cells.
Open access references
Neoplastic potential of germ cells in relation to disturbances of gonadal organogenesis and changes in karyotype. Słowikowska-Hilczer J, Romer TE, Kula K. J Androl. 2003 Mar-Apr;24(2):270-8. PMID: 12634315 [Free]
Participation of OCT3/4 and beta-catenin during dysgenetic gonadal malignant transformation. Palma I, Peña RY, Contreras A, Ceballos-Reyes G, Coyote N, Eraña L, Kofman-Alfaro S, Queipo G. Cancer Lett. 2008 May 18;263(2):204-11. PMID: 18295396
Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development. Honecker F, Kersemaekers AM, Molier M, Van Weeren PC, Stoop H, De Krijger RR, Wolffenbuttel KP, Oosterhuis W, Bokemeyer C, Looijenga LH. J Pathol. 2004 Oct;204(2):167-74. PMID: 15378486