title: Analysis of MET mRNA expression in gastric cancers using RNA in situ hybridization assay: its clinical implication and comparison with immunohistochemistry and silver in situ hybridization.
abstract: We investigated MET 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 MET mRNA expression (score ≥3) was associated with lymph node metastasis (P = .014), distant metastasis (P = .001), and higher TNM stage (P<.001). MET mRNA expression was correlated with protein expression (r = 0.398; P<.001) and gene copy number (r = 0.345; P<.001). The patients showing high-MET mRNA in primary or metastatic lesions had shorter overall survival than those showing low-MET mRNA (primary tumors, P = .002; metastatic lymph nodes, P<.001). The patients showing positive conversion of MET mRNA status in metastatic lymph node had shorter overall survival than those with no conversion (P = .011). Multivariate analysis demonstrated that high MET mRNA expression in metastatic lymph node was an independent prognostic factor for overall survival (P = .007). Therefore, this study suggests that MET mRNA expression assessed by RNA ISH could be useful as a potential marker to identify MET oncogene-addicted GC.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors.forename: Jiwoon
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors.forename: Bo Gun
authors.initials: BG
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met