title: Altered expression of p27(Kip1) -interacting cell-cycle regulators in the adult testicular germ cell tumors: potential role in tumor development and histological progression.
abstract: 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.
authors.affiliation: Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Miyai
authors.forename: Sohei
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tamai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042846:CDC2-CDC28 Kinases / Q000235:genetics / Q000378:metabolism; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005854:Germ Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018239:Seminoma / Q000235:genetics / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C475820:CCNE1 protein, human; C436291:CDKN1B protein, human; C093090:CKS1B protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019927:Cyclin E; D019394:Ki-67 Antigen; D015513:Oncogene Proteins; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D042846:CDC2-CDC28 Kinases