333 Background: The purpose of this study was to examine the immunohistochemical expression of OCT3/4, CCND2, DPPA4 and NANOG in primary non-seminomatous germ cell testicular tumors that might be associated with different entities of germ cell tumors. OCT3/4, NANOG, DPPA4 and CCND2 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells. Methods: Tissue samples of non seminoma testicular germ cell tumors including carcinoma in situ (CIS, n=10), seminoma component (n=5), embryonic carcinoma (n=20), mature teratoma (n= 7), immature teratoma (n=7), yolk sac tumor (n=5) and choriocarcinoma (n=3) were first analyzed by histological evaluation followed by selection of the appropriate tissue sections prepared from paraffin embedded testicular tissue blocks fixed with buffered formalin. To investigate immunohistochemical expression, of cancer stem cell markers samples tissues were analyzed under central pathological evaluation. Results: In CIS cells all markers were detected with a strong immunohistochemical expression suggesting that CIS cells maintain characteristics of embryonic stem cells. The invasive tumor samples, in comparison, showed a more heterogeneous expression pattern of OCT3/4, NANOG, DPPA4 and CCND2. There was an abundant expression in seminomas and embryonic carcinomas compared to a marked reduction expression in choriocarcinoma and teratomas. The expression of the markers was related to tumoral tissue differentiation. The seminomatous component and the embryonic carcinoma and undifferentiated tissues such as intratubular neoplasia presented elevated expressions. Specialized tissues such as teratoma and choriocarcinoma present low expression levels or absence of studied markers. The teratomatous subtypes do not express NANOG. The sub-type coriocarcinoma tumors do not express CCND2 and NANOG. Conclusions: The immunohistochemical expression of stem cell markers OCT3/4, NANOG, DPPA4 and CCND2 follow a specific pattern that is related to tumoral differentiation and consequent loss of pluripotency characteristics.
The spermatogonial stem cell niche in testicular germ cell tumors
