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MET in gastric cancer with liver metastasis: The relationship between MET amplification and Met overexpression in primary stomach tumors and liver metastasis
Author(s) -
Kim Han S.,
Chon Hong J.,
Kim Hyunki,
Shin SuJin,
Wacheck Volker,
Gruver Aaron M.,
Kim Jong S.,
Rha Sun Y.,
Chung Hyun C.
Publication year - 2018
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.25097
Subject(s) - metastasis , stomach , medicine , immunohistochemistry , stomach cancer , fluorescence in situ hybridization , primary tumor , cancer , adenocarcinoma , gastroenterology , pathology , cancer research , oncology , biology , gene , biochemistry , chromosome
Background and Objectives Although MET amplification/overexpression was observed in a subset of gastric cancer (GC) patients, the relationship between MET amplification/overexpression in primary GC and liver metastasis was unclear. Methods GC samples and matched liver metastases ( N = 47) were analyzed by fluorescence/silver in‐situ hybridization (FISH/SISH) and by immunohistochemistry for MET amplification and MET expression, respectively. MET‐copy number (CN) and Met expression data from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA‐STAD, N = 356) were also analyzed. Results Significant overlap existed between MET amplification and Met expression in both primary stomach tumors ( P = 0.013) and liver metastasis ( P = 0.001). In TCGA‐STAD, MET‐CN (≥4 copies) and MET expression were also positively correlated ( r = 0.761; P = 0.017). Comparative analysis revealed a strong association between MET expression and MET amplification (85% concurrence) in primary stomach tumors and matched liver metastasis. MET status in synchronous liver metastasis ( N = 36) was correlated with primary stomach tumors. However, a significant correlation between primary tumors and liver metastases was not observed in patients with metachronous liver metastasis. Survival analyses revealed that both MET amplification and MET overexpression were prognostic of poor outcomes. Conclusions MET amplification and Met overexpression were positively correlated in GC. MET status should be re‐evaluated in GC patients with liver metastasis, especially for metachronous metastasis.