Farley John, Smith Leia M, Darcy Kathleen M, Sobel Eugene, O'Connor Dennis, Henderson Benita, Morrison Larry E, Birrer Michael J
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Tripler Army Medical Center (TAMC, HI), 96859-5000, USA.
Cancer Res. 2003 Mar 15;63(6):1235-41.
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.
细胞周期蛋白E是G1期向S期转变的关键调节因子。细胞周期蛋白E表达异常与多种癌症的生存率相关。本研究评估了细胞周期蛋白E在人类卵巢癌中的预后相关性。在妇科肿瘤学组方案111治疗的患者的139例晚期、减瘤不充分的上皮性卵巢癌标本中，评估了细胞周期蛋白E的免疫组化表达。在62例（45%）晚期、减瘤不充分的卵巢癌患者中观察到高细胞周期蛋白E蛋白表达（≥40%细胞周期蛋白E阳性肿瘤细胞）。细胞周期蛋白E的表达与年龄、种族、分期、分级、细胞类型或残留病灶量无关。高细胞周期蛋白E表达与低表达相比，中位生存期较短（29±2个月对35±3个月），总生存期较差（P<0.05）。单因素和多因素回归分析显示，高细胞周期蛋白E相对于低表达与死亡风险增加40%-50%相关（风险比，P≤0.05）。在20例患者的亚组中使用荧光原位杂交检测细胞周期蛋白E基因扩增。10例高细胞周期蛋白E表达的病例中有8例显示细胞周期蛋白E基因扩增，而10例低表达的病例中只有1例显示基因扩增（P<0.006）。高细胞周期蛋白E表达是晚期卵巢癌患者独立的不良预后因素，且与细胞周期蛋白E基因扩增相关。
