Wilms 瘤蛋白 1 和雌激素受体β的表达与子宫癌肉瘤不良预后相关。

Wilms' tumor 1 protein and estrogen receptor beta expression are associated with poor outcomes in uterine carcinosarcoma.

机构信息

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine at Denver, Denver, CO, USA.

出版信息

Ann Surg Oncol. 2013 Jul;20(7):2373-9. doi: 10.1245/s10434-012-2838-9. Epub 2013 Jan 24.

DOI:10.1245/s10434-012-2838-9

PMID:23344579

Abstract

BACKGROUND

Uterine carcinosarcoma (CS) is an aggressive malignancy. Increased expression of Wilms' tumor 1 (WT1) protein and estrogen receptor beta (ER-β) protein is associated with worse outcomes in gynecologic cancers; therefore, we sought to assess this association in CS patients.

METHODS

A retrospective analysis was conducted for women diagnosed with uterine CS from departmental databases. WT1/ER-β expression was determined by immunohistochemical staining and scoring of specimens. Univariate and multivariate models were used to correlate progression-free survival (PFS) and overall survival (OS) with WT1/ER-β expression and clinicopathologic factors.

RESULTS

Ninety four patients had mean follow-up of 27 months. Postoperative treatments included chemotherapy for 52 (55 %) subjects and radiotherapy for 25 (27 %). Sixty-four (68 %) and 74 (79 %) tumor samples expressed WT1 and ER-β by immunohistochemistry, respectively. On univariate analysis, stage (p = .02) and lower uterine segment invasion (LUSI) (p = .001) were associated with decreased PFS. Only stage (p = .003) was linked to OS. In the total sample, increased WT1 expression was marginally associated with impaired PFS (p = .07) and OS (p = .09) but ER-β expression was not associated with PFS (p = .89) or OS (p = .30). WT1 and ER-β concurrent expression was associated with impaired OS (p = .02) and PFS (p = .02). On multivariate analysis, LUSI was a significant prognostic factor for PFS [hazard ratio (HR) 2.21, 95 % confidence interval (CI) = 1.12-4.32, p = .03] and stage for OS (HR 3.20, 95 % CI = 1.23-8.35, p = .02). Increased WT1/ER-β expression was associated with impaired OS (HR 1.31, 95 % CI = 1.02-1.69, p = .04).

CONCLUSIONS

Concurrent increased WT1 and ER-β expression impairs prognosis for women with uterine CS. Further research is warranted to define how relevant pathways interact and whether targeting these pathways improves OS.

摘要

背景

子宫癌肉瘤（CS）是一种侵袭性恶性肿瘤。Wilms 瘤 1（WT1）蛋白和雌激素受体β（ER-β）蛋白的表达增加与妇科癌症的不良预后相关；因此，我们试图在 CS 患者中评估这种相关性。

方法

对来自部门数据库的诊断为子宫 CS 的女性进行回顾性分析。通过免疫组织化学染色和标本评分确定 WT1/ER-β 表达。使用单变量和多变量模型将无进展生存期（PFS）和总生存期（OS）与 WT1/ER-β 表达和临床病理因素相关联。

结果

94 例患者的平均随访时间为 27 个月。术后治疗包括 52 例（55%）患者化疗和 25 例（27%）患者放疗。64（68%）和 74（79%）例肿瘤标本通过免疫组化分别表达 WT1 和 ER-β。单变量分析显示，分期（p=0.02）和下段子宫侵犯（LUSI）（p=0.001）与 PFS 降低相关。仅分期（p=0.003）与 OS 相关。在总样本中，WT1 表达增加与 PFS（p=0.07）和 OS（p=0.09）受损相关，但 ER-β 表达与 PFS（p=0.89）或 OS（p=0.30）无关。WT1 和 ER-β 同时表达与 OS（p=0.02）和 PFS（p=0.02）受损相关。多变量分析显示，LUSI 是 PFS 的重要预后因素[风险比（HR）2.21，95%置信区间（CI）=1.12-4.32，p=0.03]，而分期是 OS 的预后因素（HR 3.20，95%CI=1.23-8.35，p=0.02）。WT1/ER-β 表达增加与 OS 受损相关（HR 1.31，95%CI=1.02-1.69，p=0.04）。