Heeran Mel C, Høgdall Claus K, Kjaer Susanne K, Christensen Lise, Jensen Allan, Blaakaer Jan, Christensen Ib Jarle, Høgdall Estrid V S
Department of Pathology, Herlev Hospital, Aarhus, Denmark.
APMIS. 2013 Dec;121(12):1177-86. doi: 10.1111/apm.12071. Epub 2013 Apr 18.
The primary objective of this study was to assess the expression of MIB-1 (Ki-67) in tumour tissues from 808 patients with epithelial ovarian tumours. The second was to evaluate, whether MIB-1 (Ki-67) tissue expression levels correlate with clinicopathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the MIB-1 (Ki-67) expression levels in tissues from 202 women with borderline ovarian tumours (BOT) (177 stage I, 5 stage II, 19 stage III, 1 stage IV) and 606 ovarian cancer (OC) patients (177 stage I, 64 stage II, 311 stage III, 54 stage IV). Using a 10% cut-off level for MIB-1 (Ki-67) overexpression, 12% of the BOTs and 51% of the OCs were positive for MIB-1 (Ki-67) expression. The frequency of MIB-1 (Ki-67) expression-positive OC increased with increasing FIGO stage (p = 0.003), increasing histological grade (p ≤ 0.0001), and a significantly different distribution of MIB-1 (Ki-67) positive and negative tumours were found in adenocarcinoma NOS, serous adenocarcinomas, mucinous adenocarcinomas, endometrioid adenocarcinomas, non-epithelial and clear-cell carcinomas (p = 0.016). Univariate Kaplan-Meier survival analysis performed on all OC cases showed a significant shorter disease specific survival in patients with positive MIB-1 (Ki-67) expression in the tumour tissue (p ≤ 0.0001). In a Cox survival analysis including 606 FIGO stages I to IV OC cases, FIGO stage (II vs I: HR = 3.00, 95% CI: 1.81-4.99, III-I: HR = 6.41, 95% CI: 3.90-10.50, IV vs I: HR = 12.69, 95% CI: 7.21-22); age at diagnosis pr.10 years (HR = 1.27, 95% CI: 1.15-1.40), residual tumour after surgery (HR = 1.95, 95% CI: 1.40-2.73) and MIB-1 (Ki-67) expression (HR = 1.31, 95% CI: 1.08-1.60) had a significant independent impact on survival. Histological grade (p = 0.14) and histological tumour type (p = 0.35) had no significant independent impact on survival. In conclusion, our results predict that an increased level of MIB-1 (Ki-67) expression in tumour tissue, points to a less favourable outcome for OC patients.
本研究的主要目的是评估808例上皮性卵巢肿瘤患者肿瘤组织中MIB-1（Ki-67）的表达情况。其次是评估MIB-1（Ki-67）组织表达水平是否与该疾病的临床病理参数及预后相关。我们使用组织芯片（TA）分析了202例卵巢交界性肿瘤（BOT）患者（177例I期、5例II期、19例III期、1例IV期）和606例卵巢癌（OC）患者（177例I期、64例II期、311例III期、54例IV期）组织中的MIB-1（Ki-67）表达水平。以MIB-1（Ki-67）过表达的10%为临界值，12%的BOT和51%的OC患者MIB-1（Ki-67）表达呈阳性。MIB-1（Ki-67）表达阳性的OC患者比例随国际妇产科联盟（FIGO）分期增加（p = 0.003）、组织学分级增加（p≤0.0001）而升高，且在NOS腺癌、浆液性腺癌、黏液性腺癌、子宫内膜样腺癌、非上皮性癌和透明细胞癌中，MIB-1（Ki-67）阳性和阴性肿瘤的分布存在显著差异（p = 0.016）。对所有OC病例进行的单因素Kaplan-Meier生存分析显示，肿瘤组织中MIB-1（Ki-67）表达阳性的患者疾病特异性生存期显著缩短（p≤0.0001）。在一项纳入606例FIGO I至IV期OC病例的Cox生存分析中，FIGO分期（II期对比I期：风险比[HR]=3.00，95%置信区间[CI]：1.81 - 4.99，III期对比I期：HR = 6.41，95% CI：3.90 - 10.50，IV期对比I期：HR = 12.69，95% CI：7.21 - 22）、诊断时年龄每增加10岁（HR = 1.27，95% CI：1.15 - 1.40）、术后残留肿瘤（HR = 1.95，95% CI：1.40 - 2.73）以及MIB-1（Ki-67）表达（HR = 1.31，95% CI：1.08 - 1.60）对生存有显著独立影响。组织学分级（p = 0.14）和组织学肿瘤类型（p = 0.35）对生存无显著独立影响。总之，我们的结果表明，肿瘤组织中MIB-1（Ki-67）表达水平升高预示OC患者预后较差。
