Implication of Malignancy and Prognosis of p27kip1, Cyclin E, and Cdk2 Expression in Epithelial Ovarian Tumors

doi:10.1006/gyno.2001.6308

Gynecologic Oncology

Volume 83, Issue 1, October 2001, Pages 56-63

https://doi.org/10.1006/gyno.2001.6308 Get rights and content

Abstract

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.

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^☆: This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, and Science of Japan.

²: To whom correspondence should be addressed at Department of Physiology, Kagawa Medical University, 1750-1 Ikenobe, Miki-Cho, Kida-Gun, Kagawa 761-0793, Japan. Fax: +81-87-891-2096. E-mail: [email protected].

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Regular ArticleImplication of Malignancy and Prognosis of p27kip1, Cyclin E, and Cdk2 Expression in Epithelial Ovarian Tumors☆

Abstract

Gynecol Oncol

Cell

Cell

Gynecol Oncol

Am J Pathol

Gynecol Oncol

Gynecol Oncol

J Urol

The epidemiology of ovarian cancer

J Cell Biochem Suppl

Management of early ovarian cancer

Semin Oncol

Chemotherapy of advanced ovarian cancer

Semin Oncol

Cell cycle and cancer: critical events at the G1 restriction point

Crit Rev Oncogen

Cancer cell cycle

Science

Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution

Genes Dev

Inhibitors of mammalian G1 cyclin dependent kinases

Genes Dev

Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors

Int J Cancer

Expression of cyclin D1 correlates with malignancy in human ovarian tumours

Br J Cancer

Altered expression of cyclin D1 and CDK4 genes in ovarian carcinomas

Int J Cancer

Analysis of cyclin E and CDK2 in ovarian cancer: gene amplification and RNA overexpression

Int J Cancer

Regular Article
Implication of Malignancy and Prognosis of p27^kip1, Cyclin E, and Cdk2 Expression in Epithelial Ovarian Tumors☆