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Altered expression of p27 Kip1 ‐interacting cell‐cycle regulators in the adult testicular germ cell tumors: potential role in tumor development and histological progression
Author(s) -
Miyai Kosuke,
Yamamoto Sohei,
Iwaya Keiichi,
Asano Tomohiko,
Tamai Seiichi,
Tsuda Hitoshi,
Matsubara Osamu
Publication year - 2012
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2012.02919.x
Subject(s) - germ cell , biology , germ , cell cycle , cell , cancer research , microbiology and biotechnology , pathology , medicine , genetics , gene
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 K i‐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 IGCNU s; 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 S kp2 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 K i‐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.