Subcellular localization of p27kip1 expression predicts poor prognosis in human ovarian cancer.

Abstract

PURPOSE:

The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival.

EXPERIMENTAL DESIGN:

Subcellular localization of p27(kip1) was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27(kip1) protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma.

RESULTS:

The presence of p27(kip1) in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P < 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P < 0.0001).

CONCLUSION:

Cytoplasmic localization of p27(kip1) predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.

• Authors: Daniel G Rosen, Gong Yang, Kathy Qi Cai, Robert C Bast Jr, David M Gershenson, Elvio G Silva, Jinsong Liu
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 2 Pt 1 Pg. 632-7 (Jan 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15701850 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Tumor Suppressor Proteins
• Cyclin-Dependent Kinase Inhibitor p27

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Adenocarcinoma, Clear Cell (metabolism, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Blotting, Western
• Carcinoma, Endometrioid (metabolism, mortality, pathology)
• Cell Cycle Proteins (metabolism)
• Cell Nucleus (metabolism, pathology)
• Cyclin-Dependent Kinase Inhibitor p27
• Cytoplasm (metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Middle Aged
• Neoplasm Staging
• Neoplasms, Cystic, Mucinous, and Serous (metabolism, mortality, pathology)
• Ovarian Neoplasms (metabolism, mortality, pathology)
• Prognosis
• Subcellular Fractions (metabolism)
• Survival Rate
• Tumor Suppressor Proteins (metabolism)