Mismatch repair status and outcomes after adjuvant therapy in patients with surgically staged endometrial cancer
Mismatch repair status and outcomes after adjuvant therapy in patients with surgically staged endometrial cancer
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DOI：
10.1016/j.ygyno.2009.12.028
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发表时间：
2010-05-01
影响因子：
4.7
通讯作者：
Cohn, David E.
中科院分区：
文献类型：
--
作者：
Resnick, Kimberly E.;Frankel, Wendy L.;Cohn, David E.
目标.目的探讨DNA错配修复（MMR）是否影响子宫内膜癌患者对化疗或放疗的反应。在原发性子宫内膜癌标本的组织微阵列上进行DNA MMR蛋白MLH 1、MSH 2、MSH 6和PMS 2的免疫组织化学（IHC）。MMR缺陷被定义为缺乏一种或多种蛋白质的表达。所有蛋白质的表达将肿瘤分类为具有完整的MMR系统。计算接受铂类化疗或盆腔外照射治疗的女性的复发率。使用对数秩检验进行比较。多重比较采用Bonferroni校正法进行控制。477例子宫内膜癌的组织芯片（TMA）进行了评估。158例患者（41%）接受化疗。66例患者（17%）接受了盆腔远距离治疗。当按放疗或化疗辅助治疗分层时，肿瘤有完整MMR和有缺陷MMR的患者的总体和无进展生存期没有差异。按组织学（非类胶质瘤与类胶质瘤）和分期分层的亚组分析确实显示了显著的生存差异。与完整MMR系统的患者相比，MMR缺陷的非类胶质瘤患者接受远距离治疗的总体（p = 0.003）和无进展（p = 0.004）生存率显著增加。III/IV期完整MMR患者接受辅助化疗后，无进展生存率提高（p = 0.031）。非子宫内膜样癌和MMR缺陷的亚组患者在辅助放疗后生存率可能有所提高。晚期子宫内膜癌和错配修复缺陷的患者可能从辅助化疗中获益较少。(C)2010年爱思唯尔公司All rights reserved.
Objectives. To determine whether DNA mismatch repair (MMR) modifies the response to chemotherapy or radiotherapy in patients with endometrial cancer.Methods. Immunohistochemistry (IHC) for the DNA MMR proteins MLH1, MSH2, MSH6, and PMS2 was performed on a tissue microarray of specimens of primary endometrial cancer. MMR deficiency was defined as lack of expression of one or more proteins. Expression of all proteins classified a tumor as having an intact MMR system. Recurrence rates were calculated for women treated with platinum-based chemotherapy or pelvic external beam radiation. Comparisons were made using the log-rank test. Multiple comparisons were controlled for by utilizing the Bonferroni correction method.Results. Four hundred seventy-seven cases of endometrial cancer were evaluated on a tissue microarray (TMA). One hundred fifty-eight patients (41%) received chemotherapy. Sixty-six patients (17%) received pelvic teletherapy. Overall and progression-free survival were not different between patients whose tumors had intact MMR and those with defective MMR when stratified by adjuvant treatment with radiation or chemotherapy. Subgroup analyses stratified by histology (non-endometrioid versus endometrioid) and stage did show significant survival differences. There was a significant increase in overall (p = 0.003) and progression-free (p = 0.004) survival in those with MMR-deficient, non-endometrioid tumors treated with teletherapy compared to those with an intact MMR system. Improved progression-free survival was noted in patients with intact MMR with stage III/IV disease treated with adjuvant chemotherapy (p = 0.031).Conclusions. Subgroups of patients with non-endometrioid endometrial cancer and defective MMR may have improved survival after adjuvant radiotherapy. Patients with advanced stage endometrial cancer and defects in mismatch repair may receive less benefit from adjuvant chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.