Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer.
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.
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Zhi
Z
Peng
Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
Zhongwu
Z
Li
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Jing
J
Gao
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Ming
M
Lu
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Jifang
J
Gong
Biostatistical Science, Amgen Inc., Shanghai, China.
En-Tzu
ET
Tang
Molecular Sciences, Amgen Inc., Thousand Oaks, California.
Kelly S
KS
Oliner
Global Development, Amgen Inc., Shanghai, China.
Yong-Jiang
YJ
Hei
Medical Department, Amgen Inc., Shanghai, China.
Hui
H
Zhou
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China. lin100@medmail.com.cn.
Lin
L
Shen
D044466:Asian People / Q000235:genetics; D002681:China; D004358:Drug Therapy / Q000379:methods; D004943:Esophagogastric Junction / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met