title: Clinical significance of Skp2 expression, alone and combined with Jab1 and p27 in epithelial ovarian tumors.
abstract: We have previously demonstrated the inverse correlation of Jab1 and p27 proteins, as well as prognostic significance in epithelial ovarian carcinomas. In order to investigate Skp2 protein and its correlation with Jab1, p27, and clinical outcome, we evaluated Skp2 expression in a group of epithelial ovarian tumors. Immunohistochemical analysis was performed on 80 cases of ovarian tumors (33 benign and 47 malignant), and 26 of the 80 cases were evaluated by Western blot analysis. Immunofluorescence was carried out in the human ovarian adenocarcinoma cell line OVCAR-3. Skp2 expression was detected in 53.2% of malignant tumors and 18.2% of benign tumors. The positive ratio of Skp2 expression was increased from benign to malignant ovarian tumors (p=0.002). A negative correlation between Skp2 and p27 was found in benign and malignant ovarian tumors (p=0.006 and p<0.0001, respectively). Skp2 expression was significantly associated with high tumor grade (p=0.001), lymph node metastasis (p=0.01), and residual disease (p=0.012). Kaplan-Meier survival analysis showed that Skp2 expression was significantly associated with poor prognosis (p=0.013), and patients with Skp2(+)/Jab1(+)p27(-) expression had the worst prognosis among all phenotypes of Skp2/Jab1/p27 expression (p=0.0007). Our results suggest that Skp2 expression was significantly associated with malignancy, and the Skp2 protein level may be a valuable prognostic factor for epithelial ovarian carcinomas. Furthermore, the combined evaluation of Skp2/Jab1/p27 proteins provides important prognostic information on patients with epithelial ovarian carcinoma.
authors.affiliation: Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Sui
authors.forename: Youyi
authors.initials: Y
authors.lastname: Dong
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Fuminori
authors.initials: F
authors.lastname: Yamaguchi
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tokuda
mesh_terms: D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex