丹麦卵巢癌患者中MIB-1（Ki-67）组织蛋白表达水平的预后价值。来自“MALOVA”卵巢癌研究。

Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients. From the 'MALOVA' ovarian cancer study.

作者信息

Heeran Mel C, Høgdall Claus K, Kjaer Susanne K, Christensen Lise, Jensen Allan, Blaakaer Jan, Christensen Ib Jarle, Høgdall Estrid V S

机构信息

Department of Pathology, Herlev Hospital, Aarhus, Denmark.

出版信息

APMIS. 2013 Dec;121(12):1177-86. doi: 10.1111/apm.12071. Epub 2013 Apr 18.

DOI:10.1111/apm.12071

PMID:23594232

Abstract

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.

摘要

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。