title: Cyclin E expression is a significant predictor of survival in advanced, suboptimally debulked ovarian epithelial cancers: a Gynecologic Oncology Group study.
abstract: Cyclin E is a key regulator of the G(1)-S transition. Abnormalities in cyclin E expression have been related to survival in a variety of cancers. This study 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 (> or =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 < or = 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.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Tripler Army Medical Center (TAMC, HI), 96859-5000, USA.
authors.forename: John
authors.initials: J
authors.lastname: Farley
authors.forename: Leia M
authors.initials: LM
authors.lastname: Smith
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Eugene
authors.initials: E
authors.lastname: Sobel
authors.forename: Dennis
authors.initials: D
authors.lastname: O'Connor
authors.forename: Benita
authors.initials: B
authors.lastname: Henderson
authors.forename: Larry E
authors.initials: LE
authors.lastname: Morrison
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D019927:Cyclin E / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019927:Cyclin E