title: MET amplification, protein expression, and mutations in pulmonary adenocarcinoma.
abstract: OBJECTIVE
  MET amplification, protein expression, and splice mutations at exon 14 are known to cause dysregulation of the MET/HGF pathway. Our study aimed to confirm the relationship among MET amplification, protein expression, and mutations in pulmonary adenocarcinoma.
  
  
  METHODS
  MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH) were evaluated in 316 surgically resected lung adenocarcinomas. Patients were divided into 4 groups (IHC-negative/FISH-negative, IHC-negative/FISH-positive, IHC-positive/FISH-negative, and IHC-positive/FISH-positive), and 15-20 tumors in each group were randomly selected for mutation analyses to find splice mutations at exon 14.
  
  
  RESULTS
  An IHC score of 0-3 was found in 168 (53.2%), 71 (22.5%), 59 (18.7%), and 18 (5.7%) tumors, respectively. The mean gene copy number (GCN) was 3.56; MET FISH positivity was detected in 123 (38.9%) samples, and 26 (8.2%) of them were gene amplifications. MET amplification were significantly associated with the IHC score (P<0.001, χ(2) test). Splice mutations were identified in only 2 (2.9%) of 70 cases. One had a MET IHC score of 2 and negative FISH without amplification; The other had a MET IHC score of 0 and positive FISH without amplification. MET IHC or FISH results were not prognostic indicators of overall survival in multivariate analysis.
  
  
  CONCLUSIONS
  There is a significant relationship between MET amplification and protein expression, and selection of tumors with amplification using IHC was effective. However, because of its rarity, a selection strategy for mutated tumors is implausible using IHC or FISH.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seongyeol
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: kimdw@snu.ac.kr.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: junarplus@chol.com.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Adenocarcinoma; Gene amplification; Gene expression; MET; Mutation; Non-small-cell lung carcinoma