Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer
Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer
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DOI：
10.1016/j.humpath.2017.02.004
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发表时间：
2017-08-01
期刊：
影响因子：
3.3
通讯作者：
Wakai, Toshifumi
中科院分区：
文献类型：
--
作者：
Shimada, Yoshifumi;Yagi, Ryoma;Wakai, Toshifumi
HER 2靶向治疗被认为对KRAS密码子12/13野生型、HER 2阳性转移性结直肠癌（CRC）有效。一般而言，通过使用免疫组织化学（IHC）和荧光原位杂交（FISH）确定HER 2状态。综合基因组测序（CGS）能够检测基因突变和拷贝数改变，包括KRAS突变和HER 2扩增;然而，对CGS用于检测HER 2阳性CRC的效用知之甚少。为了评估其效用，我们回顾性研究了201例I-IV期CRC患者。使用IHC和FISH评估主要位点的HER 2状态，还使用CGS评估主要位点的HER 2扩增，并在每例患者中比较这些方法的结果。CGS成功检测到415个基因的改变，包括KRAS密码子12/13突变和HER 2扩增。59例（29%）患者存在KRAS密码子12/13突变。10例（5%）患者因HER 2 MC 3+而被诊断为HER 2阳性，相同的10例（5%）患者使用CGS评估了HER 2扩增。所有201例患者的HER 2状态和HER 2扩增结果完全相同（P < .001）。10例HER 2阳性患者中有9例为KRAS 12/13野生型，被认为是HER 2靶向治疗的可能候选者。CGS具有与IHC和FISH相同的实用性，用于检测HER 2阳性患者，这些患者是HER 2靶向治疗的候选人，并有助于精确医学和定制治疗。(C)2017作者爱思唯尔公司出版
HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 MC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P < .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment. (C) 2017 The Authors. Published by Elsevier Inc.