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Cyclin E Expression Is a Significant Predictor of Survival in Advanced, Suboptimally Debulked Ovarian Epithelial Cancers: A Gynecologic Oncology Group Study¹

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Tripler Army Medical Center (TAMC, HI), 96859-5000 [J. F.]; Department of Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523-1673 [L. M. S.]; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York 14263 [K. M. D., E. S.]; Norton Healthcare, Inc., Clinical Pathology Associates, Louisville, Kentucky 40207 [D. O.]; Vysis, Inc., Downers Grove, Illinois 60515 [L. E. M., B. H.]; and Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Rockville, Maryland 20850 [M. J. B.]

Cyclin E is a key regulator of the G₁-S transition. Abnormalities in cyclinE expression have been related to survival in a variety of cancers. Thisstudy evaluated the prognostic relevance of cyclin E in human ovarian cancer. Immunohistochemical expression of cyclin E was evaluated in 139 advanced, suboptimally debulked epithelial ovarian cancer specimens from patients treated on Gynecologic Oncology Group protocol 111. High cyclin E protein expression (40% cyclin E positive tumor cells) was seen in 62 (45%) of the advanced, suboptimally debulked ovarian cancer patients. Expression of cyclin E was not associated with age, race, stage, grade, cell type, or amount of residual disease. High verses low cyclin E expression was associated with a shorter median survival (29 ± 2 versus 35 ± 3 months) and worse overall survival (P < 0.05). Univariate and multivariate regression analyses revealed that high relative to low cyclin E was associated with a 40–50% increase in the risk of death (hazard rate, P 0.05). Fluorescence in situ hybridization was used in a subset of 20 cases to examine cyclin E gene amplification. Eight of 10 cases with high cyclin E expression exhibited amplification of the cyclin E gene, whereas only 1 of 10 cases with low expression displayed gene amplification (P < 0.006). High cyclin E expression was an independent poor prognostic factor for patients with advanced ovarian cancer, and it was associated with amplification of the cyclin E gene.

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