Altered expression of p27Kip1‐interacting cell‐cycle regulators in the adult testicular germ cell tumors: potential role in tumor development and histological progression

We examined the potential role of cell‐cycle dysregulation in the development and histological progression of adult testicular germ cell tumors (TGCTs). Expressions of p27^Kip1‐interacting cell‐cycle regulators (down‐regulation of p27^Kip1 and overexpression of Skp2, Cks1, cyclin A, and cyclin E) and Ki‐67 labeling index (LI) were immunohistochemically examined in histological components of 50 intratubular germ cell neoplasms, unclassified (IGCNUs); 74 seminomas; and 25 embryonal carcinomas, identified from 88 patients. Altered expression of p27^Kip1, Skp2, Cks1, cyclin A, and cyclin E was observed in 20%, 12%, 16%, 10%, and 24% of IGCNUs; 26%, 36%, 27%, 89%, and 23% of seminomas; and 48%, 68%, 56%, 100%, and 60% of embryonal carcinomas, respectively. A significant difference in the frequency of Skp2 and cyclin A overexpression was observed between IGCNUs and seminomas. Significantly more frequent alterations of Skp2, Cks1, and cyclin E and p27^Kip1 were detected in embryonal carcinomas than in seminomas. Alterations of all cell‐cycle regulators were significantly more frequent in embryonal carcinomas than in IGCNUs. The mean Ki‐67 LI significantly increased from IGCNU (21.2%) through seminoma (34.7%) to embryonal carcinoma (54.2%). These results suggest that alterations of the p27^Kip1‐interacting cell‐cycle regulators are common in TGCTs and may be involved in their histological progression.