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Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer.
Clin Cancer Res. 2004 Aug 01; 10(15):5168-77.CC

Abstract

PURPOSE

Dysregulation of cell cycle control, in particular G(1)-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear.

EXPERIMENTAL DESIGN

The expression of selected genes from the pRb pathway that regulates G(1)-S-phase progression, including cyclin D1, p16(Ink4a), cyclin E, p27(Kip1), p21(Waf1/Cip1), and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome.

RESULTS

Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) (P = 0.05) and p21(Waf1/Cip1) (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21(Waf1/Cip1) had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21(Waf1/Cip1) in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21(Waf1/Cip1) loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27(Kip1) and p21(Waf1/Cip1) were significantly associated with increasing tumor grade.

CONCLUSIONS

This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.

Authors+Show Affiliations

Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15297421

Citation

Bali, Anish, et al. "Cyclin D1, P53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 10, no. 15, 2004, pp. 5168-77.
Bali A, O'Brien PM, Edwards LS, et al. Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res. 2004;10(15):5168-77.
Bali, A., O'Brien, P. M., Edwards, L. S., Sutherland, R. L., Hacker, N. F., & Henshall, S. M. (2004). Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 10(15), 5168-77.
Bali A, et al. Cyclin D1, P53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer. Clin Cancer Res. 2004 Aug 1;10(15):5168-77. PubMed PMID: 15297421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. AU - Bali,Anish, AU - O'Brien,Philippa M, AU - Edwards,Lyndal S, AU - Sutherland,Robert L, AU - Hacker,Neville F, AU - Henshall,Susan M, PY - 2004/8/7/pubmed PY - 2005/3/8/medline PY - 2004/8/7/entrez SP - 5168 EP - 77 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 10 IS - 15 N2 - PURPOSE: Dysregulation of cell cycle control, in particular G(1)-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear. EXPERIMENTAL DESIGN: The expression of selected genes from the pRb pathway that regulates G(1)-S-phase progression, including cyclin D1, p16(Ink4a), cyclin E, p27(Kip1), p21(Waf1/Cip1), and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome. RESULTS: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) (P = 0.05) and p21(Waf1/Cip1) (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21(Waf1/Cip1) had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21(Waf1/Cip1) in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21(Waf1/Cip1) loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27(Kip1) and p21(Waf1/Cip1) were significantly associated with increasing tumor grade. CONCLUSIONS: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15297421/Cyclin_D1_p53_and_p21Waf1/Cip1_expression_is_predictive_of_poor_clinical_outcome_in_serous_epithelial_ovarian_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15297421 DB - PRIME DP - Unbound Medicine ER -