title: Nuclear expression of S-phase kinase-associated protein 2 predicts poor prognosis of hepatocellular carcinoma.
abstract: The S-phase kinase-associated protein 2 (Skp2), which ubiquitinates the cell cycle inhibitor p27(Kip1) and targets it for degradation, is commonly overexpressed in human cancers and is associated with poor prognosis in several cancers. The aim of this study was to investigate Skp2 expression and its clinicopathologic significance in surgically resected hepatocellular carcinomas. We collected 359 hepatocellular carcinoma samples and evaluated Skp2 protein expression in cytoplasmic and nuclear fractions by immunohistochemistry using a tissue microarray method. Among the 359 patients, nuclear expression of Skp2 was observed in 41 (10.38%), and cytoplasmic expression of Skp2 was observed in 195 (49.37%). Of the several clinicopathologic variables examined, high Edmonson-Steiner grade and early recurrence correlated with nuclear expression of Skp2 (p = 0.000 and 0.022, respectively). Cytoplasmic expression of Skp2 correlated negatively with microvascular and macrovascular invasion, tumor size, histologic grade, and overall survival. Multivariate analysis revealed that nuclear expression of Skp2 correlated with short disease-free survival. Our findings suggest that nuclear expression of Skp2 may be used as an independent predictor of poor prognosis for hepatocellular carcinoma, whereas cytoplasmic expression of Skp2 may indicate less aggressive disease.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Shin
authors.forename: Soo-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Hae-Yeon
authors.initials: HY
authors.lastname: Jeong
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.forename: Kyungbun
authors.initials: K
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D044786:S-Phase Kinase-Associated Proteins