Journal
CANCER
Volume 106, Issue 9, Pages 1925-1932Publisher
WILEY
DOI: 10.1002/cncr.21767
Keywords
ovary; immunohistochemistry; prognostic marker; cyclins; microarray analysis
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Funding
- NCI NIH HHS [P01 CA 64602-1] Funding Source: Medline
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BACKGROUND. Cyclins, cyclin dependent kinases (cdks), and their inhibitors act in combination to regulate progression through the cell cycle and often are dysregu lated in carcinoma. The authors hypothesized that cyclin E plays an important role in ovarian carcinogenesis and that its overexpression may be an indicator of a poor prognosis. METHODS: Immunohistochemical analysis of cyclin E expression was performed by image analysis in normal ovaries, cystadenomas, tumors of low malignant potential, and 405 primary ovarian carcinomas by using tissue microarray technology. RESULTS: Overexpression of cyclin E was found in 63.2% of the samples and was associated with clear cell, poorly differentiated, and serous carcinoma (P <= .001), high-grade tumors (P <= .001), late-stage disease (P = .002), age older than 60 years at the time of diagnosis (P = .04), and suboptimal cytoreduction (P = .001). A high percentage of cyclin E-expressing cells was associated with a poor outcome in univariate and in multivariate analyses. in addition, cyclin E levels also reduced survival in the late-stage disease group and in patients who underwent suboptimal debulking. CONCLUSIONS: Cyclin E was identified as an independent prognostic factor in patients with ovarian carcinoma. The accumulation of cyclin E protein may be a late event in tumorigenesis and may contribute to disease progression in these patients.
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