Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma.
Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma.
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DOI：
10.3892/ijo.2013.1830
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发表时间：
2013-04
影响因子：
5.2
通讯作者：
Nishio K
中科院分区：
文献类型：
--
作者：
Kato H;Arao T;Matsumoto K;Fujita Y;Kimura H;Hayashi H;Nishiki K;Iwama M;Shiraishi O;Yasuda A;Shinkai M;Imano M;Imamoto H;Yasuda T;Okuno K;Shiozaki H;Nishio K
分子靶向治疗有望成为治疗食管鳞状细胞癌（ESCC）的一种有前景的治疗方法；然而，分子靶基因在ESCC中的基因扩增状态仍不清楚。采用实时pcr技术检测245例经福尔马林固定、石蜡包埋的ESCC手术标本的EGFR、HER2、FGFR2和MET基因扩增情况。荧光原位杂交（FISH）和比较基因组杂交分析验证了拷贝数测定的结果。采用Scorpions-ARMS法检测EGFR突变。然后在体外评估EGFR状态和对EGFR酪氨酸激酶抑制剂的药物敏感性。EGFR和HER2基因扩增在7%（16/244）和11%（27/245）的ESCC标本中观察到。一项多变量分析显示，HER2扩增是III期ESCC术后患者预后不良的重要预测因子。在8个ESCC细胞系中发现1个L861Q型EGFR突变对EGFR酪氨酸激酶抑制剂过敏，在107个临床样本中发现1个del745型EGFR突变。此外，我们首次证明在4%（8/196）的ESCC标本中观察到FGFR2扩增。MET扩增率为1%（2/196）。综上所述，ESCC标本中EGFR、HER2和FGFR2基因扩增频繁，EGFR突变活跃。我们的研究结果有力地鼓励了ESCC分子靶向治疗的发展。
Molecular targeted therapy is expected to be a promising therapeutic approach for the treatment of esophageal squamous cell carcinoma (ESCC); however, the gene amplification status of molecular targeted genes in ESCC remains largely unclear. The gene amplification of EGFR, HER2, FGFR2 and MET was examined using a real-time PCR-based copy number assay of 245 ESCC surgical specimens of formalin-fixed, paraffin-embedded samples. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization analyses verified the results of the copy number assay. EGFR mutation was detected using the Scorpions-ARMS method. The EGFR status and drug sensitivity to an EGFR tyrosine kinase inhibitor was then evaluated in vitro. Gene amplification of EGFR and HER2 was observed in 7% (16/244) and 11% (27/245) of the ESCC specimens. A multivariate analysis revealed that HER2 amplification was a significant predictor of a poor prognosis in patients with stage III post-operative ESCC. The L861Q type of EGFR mutation with hypersensitivity to EGFR tyrosine kinase inhibitor was found in one of the eight ESCC cell lines and one del745 type of EGFR mutation was identified in 107 clinical samples. In addition, we demonstrated for the first time that FGFR2 amplification was observed in 4% (8/196) of the ESCC specimens. MET amplification was observed in 1% (2/196). In conclusion, the frequent gene amplification of EGFR, HER2 and FGFR2 and the presence of active EGFR mutations were observed in ESCC specimens. Our results strongly encourage the development of molecular targeted therapy for ESCC.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
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158.5
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Bonner, JA;Harari, PM;Ang, KK
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Ang, KK
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Takeda, Masayuki;Arao, Tokuzo;Nishio, Kazuto
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Nishio, Kazuto
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20.4
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Duyster, Justus
影响因子：
56.9
作者：
Paez, JG;Jänne, PA;Meyerson, M
通讯作者：
Meyerson, M