Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours
Article first published online: 27 JUN 2005
Volume 47, Issue 1, pages 48–56, July 2005
How to Cite
Hoei-Hansen, C. E., Almstrup, K., Nielsen, J. E., Brask Sonne, S., Graem, N., Skakkebaek, N. E., Leffers, H. and Rajpert-De Meyts, E. (2005), Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. Histopathology, 47: 48–56. doi: 10.1111/j.1365-2559.2005.02182.x
- Issue published online: 27 JUN 2005
- Article first published online: 27 JUN 2005
- Date of submission 30 December 2004 Accepted for publication 23 February 2005
- intratubular germ cell neoplasia;
- testicular germ cell cancer;
- testicular intraepithelial neoplasia;
Aims : NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens.
Methods and results : We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring earlier than for OCT-4. We detected no expression at the protein level in normal testis.
Conclusions : NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG down-regulation in fetal gonocytes suggests that NANOG may act as a regulatory factor up-stream to OCT-4.