ERCC1、p53 和 III 类 β-微管蛋白的表达不能揭示子宫内膜癌的化疗耐药性：免疫组织化学研究结果。

Expression of ERCC1, p53, and class III β-tubulin do not reveal chemoresistance in endometrial cancer: results from an immunohistochemical study.

机构信息

Department of Pathology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.

出版信息

Int J Gynecol Cancer. 2011 Aug;21(6):1071-7. doi: 10.1097/IGC.0b013e318218f28b.

DOI:10.1097/IGC.0b013e318218f28b

PMID:21792013

Abstract

BACKGROUND

In non-small cell lung cancer, expression of excision repair cross-complementation group 1 (ERCC1) and p53 correlates with platinum resistance and class III β-tubulin with resistance to taxanes. The potential to personalize treatment in endometrial cancer remains uninvestigated.

METHODS

Patients received platinum-based chemotherapy, with or without paclitaxel. Patients were divided into 2 groups: group A (n = 33) consisted of patients with early-stage endometrial cancer treated with adjuvant chemotherapy. Group B (n = 116) included cases with primary advanced or recurrent disease. Immunohistochemistry was performed to analyze the expression of ERCC1 and p53, for all cases, and class III β-tubulin for cases treated with paclitaxel. The findings were correlated with response according to Response Criteria in Solid Tumors; recurrence-free, disease-specific survival; and established prognostic markers.

RESULTS

The mean age of 149 patients was 64 years (range, 31-84 years). Distribution of histopathologic subtypes was as follows: 44 endometrioid (30%), 92 serous/clear cell (62%), and 13 carcinosarcomas (8%).In group A, 11 (33%) and 19 patients (58%) showed expression for ERCC1 and p53, respectively. Seven (78%) of nine patients receiving paclitaxel were positive for class III β-tubulin. There was no correlation between expression of ERCC1, p53, or class III β-tubulin and recurrence or survival. In group B, 25 (22%) and 61 patients (64%) were positive for ERCC1 and p53, respectively. Fifty-two (74%) of seventy patients receiving paclitaxel were positive for class III β-tubulin. Only p53 expression correlated with survival (P = 0.01).

CONCLUSIONS

In contrast to theoretical assumptions, the current study did not reveal evidence that the expression of ERCC1 and class III β-tubulin predicts response to cytotoxic treatment and patient outcome in endometrial cancer.

摘要

背景

在非小细胞肺癌中，切除修复交叉互补基因 1（ERCC1）和 p53 的表达与铂类耐药相关，而 III 类β-微管蛋白与紫杉烷类耐药相关。在子宫内膜癌中，个性化治疗的潜力尚未得到研究。

方法

患者接受铂类为基础的化疗，联合或不联合紫杉醇。患者分为 2 组：A 组（n=33）由接受辅助化疗的早期子宫内膜癌患者组成。B 组（n=116）包括原发性晚期或复发性疾病的病例。对所有病例进行 ERCC1 和 p53 的免疫组织化学分析，对接受紫杉醇治疗的病例进行 III 类β-微管蛋白分析。根据实体瘤反应标准、无复发生存、疾病特异性生存以及既定的预后标志物来分析结果与反应之间的相关性。

结果

149 例患者的平均年龄为 64 岁（范围，31-84 岁）。组织病理学亚型分布如下：44 例子宫内膜样（30%）、92 例浆液/透明细胞（62%）和 13 例癌肉瘤（8%）。A 组中，11 例（33%）和 19 例（58%）患者的 ERCC1 和 p53 表达分别为阳性。9 例接受紫杉醇治疗的患者中，有 7 例（78%）III 类β-微管蛋白阳性。ERCC1、p53 或 III 类β-微管蛋白的表达与复发或生存无相关性。B 组中，25 例（22%）和 61 例（64%）患者的 ERCC1 和 p53 表达分别为阳性。70 例接受紫杉醇治疗的患者中，有 52 例（74%）III 类β-微管蛋白阳性。只有 p53 表达与生存相关（P=0.01）。