Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer

Amanda Psyrri, Aris Bamias, Ziwei Yu, Paul Maurice Weinberger, Mohamad Kassar, Sophia Markakis, Diane Kowalski, Eleni Efstathiou, Robert L. Camp, David L. Rimm, Meletios A. Dimopoulos

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Purpose: p27 protein is regarded as a valuable prognostic biomarker in cancer with a potential use as a molecular target. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of p27 in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Experimental Design: A tissue array composed of 150 advanced stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of p27 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis [automated quantitative analysis (AQUA)]. Results: The mean follow-up time of the patients was 34.3 months. Patients with low Fédération Internationale des Gynaecologistes et Obstetristes stage were more likely to have low nuclear p27 expression (P = 0.008). Low nuclear p27 expression was associated with improved 3-year overall survival (66% versus 20%, P = 0.0047) and disease-free survival (27% versus 12%, P = 0.022). In multivariable analysis, adjusting for well-characterized prognostic variables, low nuclear p27 expression level was the most significant prognostic factor for both disease-free and overall survival. Conclusions: Our results indicate that quantitative assessment of nuclear p27 expression level by automated in situ quantitative analysis is a strong predictor for outcome in ovarian cancer.

Original languageEnglish (US)
Pages (from-to)8384-8390
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number23
DOIs
StatePublished - Dec 1 2005

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Cyclin-Dependent Kinase Inhibitor p27
Ovarian Neoplasms
Survival
Disease-Free Survival
Proteins
Tumor Biomarkers
Paclitaxel
Combination Drug Therapy
Platinum
Fluorescent Antibody Technique
Research Design
Ovarian epithelial cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer. / Psyrri, Amanda; Bamias, Aris; Yu, Ziwei; Weinberger, Paul Maurice; Kassar, Mohamad; Markakis, Sophia; Kowalski, Diane; Efstathiou, Eleni; Camp, Robert L.; Rimm, David L.; Dimopoulos, Meletios A.

In: Clinical Cancer Research, Vol. 11, No. 23, 01.12.2005, p. 8384-8390.

Research output: Contribution to journalArticle

Psyrri, A, Bamias, A, Yu, Z, Weinberger, PM, Kassar, M, Markakis, S, Kowalski, D, Efstathiou, E, Camp, RL, Rimm, DL & Dimopoulos, MA 2005, 'Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer', Clinical Cancer Research, vol. 11, no. 23, pp. 8384-8390. https://doi.org/10.1158/1078-0432.CCR-05-1270
Psyrri, Amanda ; Bamias, Aris ; Yu, Ziwei ; Weinberger, Paul Maurice ; Kassar, Mohamad ; Markakis, Sophia ; Kowalski, Diane ; Efstathiou, Eleni ; Camp, Robert L. ; Rimm, David L. ; Dimopoulos, Meletios A. / Subcellular localization and protein levels of cyclin-dependent kinase inhibitor p27 independently predict for survival in epithelial ovarian cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 23. pp. 8384-8390.
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AU - Markakis, Sophia

AU - Kowalski, Diane

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N2 - Purpose: p27 protein is regarded as a valuable prognostic biomarker in cancer with a potential use as a molecular target. However, different methods of immunohistochemical assessment have yielded conflicting results. Here, we sought to determine the prognostic value of p27 in ovarian cancer using a novel method of compartmentalized in situ protein analysis. Experimental Design: A tissue array composed of 150 advanced stage ovarian cancers uniformly treated, with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of p27 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis [automated quantitative analysis (AQUA)]. Results: The mean follow-up time of the patients was 34.3 months. Patients with low Fédération Internationale des Gynaecologistes et Obstetristes stage were more likely to have low nuclear p27 expression (P = 0.008). Low nuclear p27 expression was associated with improved 3-year overall survival (66% versus 20%, P = 0.0047) and disease-free survival (27% versus 12%, P = 0.022). In multivariable analysis, adjusting for well-characterized prognostic variables, low nuclear p27 expression level was the most significant prognostic factor for both disease-free and overall survival. Conclusions: Our results indicate that quantitative assessment of nuclear p27 expression level by automated in situ quantitative analysis is a strong predictor for outcome in ovarian cancer.

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