Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer
Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer
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DOI：
10.1016/j.clcc.2018.05.006
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发表时间：
2018-09-01
影响因子：
3.4
通讯作者：
Fujii, Satoshi
中科院分区：
文献类型：
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作者：
Sawada, Kentaro;Nakamura, Yoshiaki;Fujii, Satoshi
我们评估了转移性结直肠癌中人表皮生长因子受体2（HER 2）扩增的预后影响以及抗表皮生长因子受体（EGFR）治疗的疗效。HER 2扩增与RAS或BRAF（V600 E）突变一样是转移性结直肠癌患者总生存期的潜在预后因素，也是抗EGFR治疗的潜在阴性预测因子。目的：评价HER 2扩增对转移性结直肠癌（mCRC）患者的预后和预测价值。患者与方法：纳入了在2005年至2015年期间接受原发肿瘤手术切除术并接受最佳支持治疗伴或不伴姑息化疗的mCRC患者。使用福尔马林固定、石蜡包埋的原发性肿瘤标本进行HER 2免疫组织化学。通过荧光原位杂交证实HER 2扩增。使用基于PCR的方法集中评估RAS和BRAF（V600 E）突变。患者分为4个亚组：R（RAS突变）、B（BRAF（V600 E）突变）、H（伴HER 2扩增的野生型RAS/BRAF）和W（不伴HER 2扩增的野生型RAS/BRAF）。评估抗表皮生长因子受体（EGFR）治疗的总生存期（OS）和无进展生存期。结果：在370例符合条件的患者中，成功分析了359例数据。15个肿瘤具有HER 2扩增，包括4个伴有RAS突变的肿瘤（R组）。R、B、H和W组的患者数量分别为204、13、11和131例。中位OS为27.4个月，中位随访时间为63.2个月。R、B、H和W组的中位OS分别为24.0、14.2、19.9和39.1个月。R、B、H和W组中接受抗EGFR治疗的患者数量分别为17、4、5和49例。R、B和H组抗EGFR治疗的无进展生存期显著短于W组。结论：HER 2扩增可预测抗EGFR治疗反应，并似乎是mCRC患者的预后。(C)2018爱思唯尔公司All rights reserved.
We evaluated the prognostic impact of human epidermal growth factor receptor 2 (HER2) amplification in metastatic colorectal cancer as well as the efficacy of antie-epidermal growth factor receptor (EGFR) therapy. HER2 amplification was as potentially prognostic for overall survival as RAS or BRAF(V600E) mutation as well as a potential negative predictive factor of anti-EGFR therapy in metastatic colorectal cancer.Purpose: To evaluate a prognostic and predictive value of HER2 amplification in patients with metastatic colorectal cancer (mCRC). Patients and Methods: Patients with mCRC who underwent surgical resection of the primary tumor and who received best supportive care with or without palliative chemotherapy between 2005 and 2015 were included. HER2 immunohistochemistry was performed using formalin-fixed, paraffin-embedded primary tumor specimens. HER2 amplification was confirmed by fluorescence in-situ hybridization. The RAS and BRAF(V600E) mutations were centrally assessed using a PCR-based method. Patients were divided into 4 subgroups: R (RAS mutant), B (BRAF(V600E) mutant), H (wild-type RAS/BRAF with HER2 amplification), and W (wild-type RAS/BRAF without HER2 amplification). Overall survival (OS) and progression-free survival of antie-epidermal growth factor receptor (EGFR) therapy were assessed. Results: Among 370 eligible patients, data of 359 were successfully analyzed. Fifteen tumors harbored HER2 amplifications, including 4 tumors with concomitant RAS mutation (group R). The number of patients in groups R, B, H, and W was 204, 13, 11, and 131, respectively. The median OS was 27.4 months, and the median follow-up time was 63.2 months. The median OS for groups R, B, H, and W was 24.0, 14.2, 19.9, and 39.1 months, respectively. The number of patients who received anti-EGFR therapy in groups R, B, H, and W was 17, 4, 5, and 49, respectively. Progression-free survival of anti-EGFR therapy was significantly shorter in groups R, B, and H than in group W. Conclusion: HER2 amplification was predictive of anti-EGFR therapy response and appeared to be prognostic in mCRC patients. (C) 2018 Elsevier Inc. All rights reserved.