Immunohistochemical expression of four different stem cell markers in prostate cancer: High expression of NANOG in conjunction with hypoxia-inducible factor-1α expression is involved in prostate epithelial malignancy

Cancer stem cells (CSCs) have been identified in a variety of cancer types, including prostate cancer. The aim of the present study was to evaluate the immunohistochemical expression of NANOG, octamer 4 (OCT4), cluster of differentiation 133 (CD133) and NESTIN, which are all CSC markers, and assess their function in prostate carcinogenesis. A total of 114 patients were referred to the Kanazawa Medical University Hospital (Uchinada, Japan) having presented with elevated serum prostate-specific antigen levels and/or abnormal digital rectal examinations, and underwent transrectal ultrasound sonography guided eight core biopsies. The prostate pathological specimens were re-evaluated for selection in this study. When specimens were diagnosed as prostate cancer, immunohistochemical analysis of the four different stem cell markers (NANOG, OCT4, CD133 and NESTIN) and hypoxia-inducible factor (HIF)-1 alpha was performed. Prostate cancer was found in 38 cases (33.3%), while the other patients had benign prostate hyperplasia with prostatitis. All prostate cancers were histopathologically identified as adenocarcinomas of various grades, and cancer cells and intraepithelial neoplasia (high grade) were immunohistochemically shown to express NANOG and OCT4, but not CD 133 and NESTIN. The intensity of NANOG expression was much greater than that of OCT4, and the positivity and intensity of the four stem cell markers, including NANOG, were elevated with high Gleason scores. A significant correlation was observed between the NANOG- and HIF-1 alpha-positive regions. The CSC markers, in particular OCT4 and NANOG, were immunohistochemically expressed in prostate cancers. Furthermore, HIF-1 alpha expression may affect NANOG and/or OCT4 expression. The findings of the current study suggested that NANOG expression may be a biomarker for the diagnosis of prostate cancer, and the coexpression of NANOG and HIF-1 alpha may be involved in prostate carcinogenesis.