威尔姆斯瘤1（WT1）蛋白的表达水平在上皮性卵巢癌中的预后价值有限：来自丹麦“MALOVA”卵巢癌研究。

Expression level of Wilms tumor 1 (WT1) protein has limited prognostic value in epithelial ovarian cancer: from the Danish "MALOVA" ovarian cancer study.

作者信息

Høgdall Estrid V S, Christensen Lise, Kjaer Susanne K, Blaakaer Jan, Christensen Ib Jarle, Gayther Simon, Jacobs Ian J, Høgdall Claus K

机构信息

Department of Virus, Hormones and Cancer, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.

出版信息

Gynecol Oncol. 2007 Aug;106(2):318-24. doi: 10.1016/j.ygyno.2007.03.043. Epub 2007 May 31.

DOI:10.1016/j.ygyno.2007.03.043

PMID:17540436

Abstract

OBJECTIVES

To determine the WT1 expression level in tumor tissues from 774 women with an epithelial ovarian tumor. Secondly, to evaluate whether WT1 tissue expression levels correlate with clinico-pathological parameters and finally to investigate the prognostic value of WT1 expression levels in ovarian cancer (OC) patients.

METHODS

Using tissue array we analyzed the WT1 expression level in tissues from 186 women with Low Malignant Potential tumors (LMP) (160 stage I, 5 stage II and 21 stage III) and 560 OC patients (160 stage I, 60 stage II, 289 stage III and 51 stage IV).

RESULTS

Using 10% as cut-off level for WT1 overexpression an overall of 19% LMPs and 17% carcinomas, respectively, were found positive. For both, a higher proportion of positive tumors was found in the serous subtype compared to other histological subtypes (p<0.0001). Kaplan-Meier survival analysis stratified by FIGO stage performed on cases using a 10% cut-off showed a shorter disease specific survival in patients with a positive WT1 expression in the tumor tissue. In a Cox survival analysis including 559 stage I to IV OC prognostic factors included FIGO stage (II vs. I: HR=2.74, 95% CI: 1.42-5.29; III vs. II: HR=2.23, 95% CI: 1.49-3.36; IV vs. III: HR=1.75, 95% CI: 1.25-2.44), residual tumor after primary surgery (HR=2.82, 95% CI: 1.87-4.26), age at diagnosis (HR=1.02, 95% CI: 1.01-1.03), histological grade 3 of tumor versus grade 1 (grade 2 vs. grade 1: HR=1.31, 95% CI: 0.95-1.81; grade 3 vs. grade 1: HR=1.51, 95% CI: 1.08-2.09) and other histological tumor types vs. serous (mucinous vs. serous: HR=0.91, 95% CI: 0.53-1.56; endometrioid vs. serous: HR=1.02, 95% CI: 0.69-1.50; other histological types vs. serous: HR=1.40, 95% CI: 1.01-1.95). WT1 expression (HR=1.22, 95% CI: 0.94-1.59) had statistically no significant independent impact on survival.

CONCLUSION

In conclusion, based on our analyses we found that WT1 expression in clinical settings may be of limited prognostic value in Danish OC patients.

摘要

目的

确定774例上皮性卵巢肿瘤女性患者肿瘤组织中的WT1表达水平。其次，评估WT1组织表达水平是否与临床病理参数相关，最后研究WT1表达水平在卵巢癌（OC）患者中的预后价值。

方法

我们使用组织芯片分析了186例低恶性潜能肿瘤（LMP）患者（160例I期、5例II期和21例III期）以及560例OC患者（160例I期、60例II期、289例III期和51例IV期）组织中的WT1表达水平。

结果

以WT1过表达的10%为临界值，分别发现19%的LMP和17%的癌呈阳性。与其他组织学亚型相比，浆液性亚型中阳性肿瘤的比例更高（p<0.0001）。对使用10%临界值的病例按国际妇产科联盟（FIGO）分期进行的Kaplan-Meier生存分析显示，肿瘤组织中WT1表达阳性的患者疾病特异性生存期较短。在一项包括559例I至IV期OC患者的Cox生存分析中，预后因素包括FIGO分期（II期与I期：风险比[HR]=2.74，95%置信区间[CI]：1.42 - 5.29；III期与II期：HR=2.23，95% CI：1.49 - 3.36；IV期与III期：HR=1.75，95% CI：1.25 - 2.44）、初次手术后残留肿瘤（HR=2.82，95% CI：1.87 - 4.26）、诊断时年龄（HR=1.02，95% CI：1.01 - 1.03）、肿瘤组织学3级与1级相比（2级与1级：HR=1.31，95% CI：0.95 - 1.81；3级与1级：HR=1.51，95% CI：1.08 - 2.09）以及其他组织学肿瘤类型与浆液性相比（黏液性与浆液性：HR=0.91，95% CI：0.53 - 1.56；子宫内膜样与浆液性：HR=1.02，95% CI：0.69 - 1.50；其他组织学类型与浆液性：HR=1.40，95% CI：1.01 - 1.95）。WT1表达（HR=1.22，95% CI：0.94 - 1.59）对生存无统计学上的显著独立影响。