Sun Yat-Sen University Cancer Center, Guangzhou, China
Rui-hua Xu , Miaozhen Qiu , Yi-xin Zhou , De-Shen Wang , Dong-sheng Zhang , Fenghua Wang , Yu-hong Li , Jacqueline Huang , Hui Zhou , En-Tzu Tang , Zhiqiang Du , Fanny Zhang
Background: Gastric cancer is a disease with high unmet medical needs in China. MET and its ligand, hepatocyte growth factor, are potential targets in G/GEJ cancer. This study evaluated overall survival (OS) according to tumor MET expression, MET gene amplification, and the association between MET and HER2 status in Chinese patients with advanced G/GEJ cancer. Methods: Baseline tumor biopsy samples (formalin-fixed, paraffin-embedded primary tumor) from patients with stage IV unresectable G/GEJ cancer, archived at Sun Yat-Sen University Cancer Center, were assessed for MET and HER2 protein levels and MET and HER2 gene amplification by IHC and FISH, respectively. MET-positive: membrane protein staining in ≥ 25% or ≥ 50% of tumor cells. HER2-positive: IHC 2+ and a confirmatory HER2 FISH-positive result (HER2:centromere 17 ratio ≥ 2.0), or IHC 3+. MET-amplified: MET:centromere 7 ratio > 2.0. We evaluated associations between Kaplan-Meier OS and MET status (log-rank test), MET expression and METgene amplification, and MET and HER2 status (Fisher exact test). Results: Of 289 eligible patients, 271 had evaluable IHC samples, and MET-positive rates were 42.1% and 25.1% by 25% and 50% cutoffs, respectively. Median OS by different levels of MET-positive expression is shown in the Table. Of 183 patients with evaluable FISH samples, 8 (4.4%) were MET-amplified. In 171 patients with IHC and FISH data, MET-positive expression by 25% and 50% cutoffs was associated with MET amplification (P < 0.005, both cutoffs). In 145 patients with MET IHC, FISH, and HER2 data, the HER2-positive rate was 13.8%. Of patients who were MET-positive by 25% and 50% cutoffs, 8/48 (16.7%) and 4/29 (13.8%), respectively, were also HER2-positive. Additionally, 1/8 (12.5%) MET-amplified patients was HER2-positive. Conclusions: MET-positive status was associated with shorter OS in this population of Chinese patients with advanced G/GEJ cancer. MET high expression or MET amplification was not associated with HER2 expression.
Patients evaluable for IHC | MET-positive | MET-negative | P value |
---|---|---|---|
25% cutoff | |||
n | 114 | 157 | |
OS, mo* | 10.9 | 16.0 | 0.054 |
50% cutoff | |||
n | 68 | 203 | |
OS, mo* | 8.3 | 15.5 | < 0.001 |
*Median
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