MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors
MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors
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DOI：
10.1530/erc-16-0117
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发表时间：
2016-08-01
影响因子：
3.9
通讯作者：
Couvelard, A.
中科院分区：
文献类型：
--
作者：
Cros, J.;Hentic, O.;Couvelard, A.
替莫唑胺(TEM)治疗分化良好的胰腺神经内分泌肿瘤(WDPNETs)显示令人鼓舞的结果。肿瘤内低表达的O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)和MGMT启动子甲基化与基于透射电子显微镜化疗的胶质母细胞瘤较好的预后相关。我们的目的是评估MGMT表达和MGMT启动子甲基化是否有助于预测WDPNET患者基于透射电子显微镜的化疗的疗效。对2006-2012年间连续接受TEM术的进展性WDPNET和/或肝脏受累超过50%的患者进行了回顾性研究。根据实体肿瘤反应评估标准(RECIST)1.1指南评估肿瘤反应。免疫组化法检测MGMT的核表达(H-Score，0~300)，焦磷酸测序法检测MGMT启动子的甲基化。分析43例WDPNET 1级(6例)或2级(36例)患者，男性21例，年龄58岁(27~84岁)。目的：缓解17例(39.5%)，病情稳定18例(41.9%)，进展8例(18.6%)。低MGMT表达(
Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O-6-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58 years (27-84)) with grade 1 WDPNET (n = 6) or 2 (n = 36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (