Analysis of <i>MET</i> mRNA Expression in Gastric Cancers Using RNA In Situ Hybridization Assay: Its Clinical Implication and Comparison with Immunohistochemistry and Silver In Situ Hybridization

<div><p>We investigated <i>MET</i> mRNA expression status using RNA in situ hybridization (ISH) technique in primary and metastatic lesions of 535 surgically resected gastric carcinoma (GC) cases. We compared the results with those of immunohistochemistry and silver in situ hybridization, and examined the association with clinicopathologic characteristics and prognosis. Among 535 primary GCs, 391 (73.1%) were scored 0, 87 (16.3%) were scored 1, 38 (7.1%) were scored 2, 12 (2.2%) were scored 3 and 7 (1.3%) were scored 4 by RNA ISH. High <i>MET</i> mRNA expression (score ≥3) was associated with lymph node metastasis (<i>P</i> = .014), distant metastasis (<i>P</i> = .001), and higher TNM stage (<i>P</i><.001). <i>MET</i> mRNA expression was correlated with protein expression (r = 0.398; <i>P</i><.001) and gene copy number (r = 0.345; <i>P</i><.001). The patients showing high-<i>MET</i> mRNA in primary or metastatic lesions had shorter overall survival than those showing low-<i>MET</i> mRNA (primary tumors, <i>P</i> = .002; metastatic lymph nodes, <i>P</i><.001). The patients showing positive conversion of <i>MET</i> mRNA status in metastatic lymph node had shorter overall survival than those with no conversion (<i>P</i> = .011). Multivariate analysis demonstrated that high <i>MET</i> mRNA expression in metastatic lymph node was an independent prognostic factor for overall survival (<i>P</i> = .007). Therefore, this study suggests that <i>MET</i> mRNA expression assessed by RNA ISH could be useful as a potential marker to identify <i>MET</i> oncogene-addicted GC.</p></div>