Implication of malignancy and prognosis of p27(kip1), Cyclin E, and Cdk2 expression in epithelial ovarian tumors.
OBJECTIVE
The aim of this study was to further evaluate whether the expression of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovarian tumors and whether their expressions, alone or in combination, are associated with prognosis in epithelial ovarian carcinoma.


METHODS
Immunohistochemical analysis using anti-p27(kip1), anti-cyclinE, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign, borderline, and malignant ovarian tumors, and Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian tumor samples.


RESULTS
p27(kip1) expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradually increased from benign to borderline to malignant tumors. Kaplan-Meier survival analysis showed that patients with p27(kip1) expression had a high overall survival rate. Patients with cyclin E overexpression had a low overall survival rate. When the combination of these proteins was analyzed, patients with the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were significantly associated with the poorest overall survival. In multivariate Cox regression analysis, the combined phenotype of p27(kip1) (-)/cyclin E (++)/cdk2 (++) was independently related to poor prognosis.


CONCLUSIONS
Our results suggest that loss of p27(kip1) expression and overexpression of cyclin E or cdk2 were significantly associated with malignancy in ovarian tumors. p27(kip1) and cyclin E proteins may be valuable prognostic factors for epithelial ovarian carcinoma patients. Furthermore, the combined evaluation of p27(kip1)/cyclin E/cdk2 may provide the most important prognostic implication.
Sui
L
L
Department of Perinato-Gynecology, Kagawa Medical University, Kagawa 761-0793, Japan.
Dong
Y
Y
Ohno
M
M
Sugimoto
K
K
Tai
Y
Y
Hando
T
T
Tokuda
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D019927:Cyclin E / Q000096:biosynthesis*; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D019927:Cyclin E; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases