Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer
复制标题
中国局部晚期或转移性胃癌或胃食管结合部癌患者的肿瘤 MET 表达和基因扩增
DOI：
10.1158/1535-7163.mct-15-0108
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发表时间：
2015-11-01
影响因子：
5.7
通讯作者：
Shen, Lin
中科院分区：
文献类型：
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作者：
Peng, Zhi;Li, Zhongwu;Shen, Lin
MET及其唯一配体肝细胞生长因子(HGF)是治疗胃和胃食道交界癌的有前景的靶点。我们评估了MET蛋白表达或MET基因扩增是否可以预测中国晚期胃或胃食道交界区癌症患者的总生存期(OS)。2008年至2010年在北京大学肿瘤医院参加临床试验的不能切除的局部晚期或转移性胃或胃食道交界部癌患者的福尔马林固定、石蜡包埋的肿瘤标本通过免疫组织化学和FISH方法检测MET和P-MET的表达。MET阳性表达定义为≥中25%的肿瘤细胞膜蛋白染色。MET扩增定义为MET：着丝粒7比2.0。我们测试了MET状态与临床特征和OS的关联，并评估了表达和扩增之间的关联。168名患者符合条件。在可评估的样本中，137份样本中有53份(39%)MET阳性，134份样本中有8份(6%)p-MET阳性，113份样本中有8份(7%)MET扩增。除Lauren分级外，MET表达和MET扩增均与临床特征无关(P=0.04)，MET扩增与弥漫型相关。无论是否接受一线化疗，MET阳性和MET阴性人群之间的OS没有显著差异。在95名可评估的患者中，MET的表达与MET的扩增显著相关(P<；0.001)；所有MET扩增的肿瘤样本都有部分MET的表达。在96例可评估的患者中，p-MET阳性与MET扩增显著相关(P<；0.001)。为了证实我们的发现，有必要在更大和独立的样本集中进行进一步的评估。摩尔癌症杂志；14(11)；2634-41。©2015年AACR。
MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or MET gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and MET amplification by FISH. MET-positive expression was defined as membrane protein staining in ≥25% of tumor cells. MET amplification was defined as MET:centromere 7 ratio >2.0. We tested the association of MET status with clinical characteristics and OS, and also evaluated the association between expression and amplification. One hundred sixty-eight patients were eligible. Of the evaluable samples, 53 of 137 (39%) were MET positive, eight of 134 (6%) were p-MET positive, and eight of 113 (7%) were MET amplified. Neither MET expression nor MET amplification were associated with clinical characteristics, except Lauren classification (P = 0.04); MET amplification was associated with diffuse type. No significant OS difference was observed between MET-positive and MET-negative populations, regardless of first-line chemotherapy received. In 95 evaluable patients, MET expression was significantly associated with MET amplification (P < 0.001); all MET-amplified tumor samples showed some MET expression. In 96 evaluable patients, p-MET positivity was significantly associated with MET amplification (P < 0.001). Further evaluation in larger and independent sample sets is warranted to confirm our findings. Mol Cancer Ther; 14(11); 2634–41. ©2015 AACR.