PMID- 26791796
OWN - NLM
STAT- MEDLINE
DCOM- 20161013
LR  - 20190221
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 90
IP  - 3
DP  - 2015 Dec
TI  - MET amplification, protein expression, and mutations in pulmonary adenocarcinoma.
PG  - 381-7
LID - S0169-5002(15)30091-X [pii]
LID - 10.1016/j.lungcan.2015.10.022 [doi]
AB  - OBJECTIVES: 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. MATERIALS AND 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, chi(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. CONCLUSION: 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.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Park, Seongyeol
AU  - Park S
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Koh, Jaemoon
AU  - Koh J
AD  - Department of Pathology, Seoul National University Hospital, Seoul, Republic of 
      Korea.
FAU - Kim, Dong-Wan
AU  - Kim DW
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea. Electronic address: kimdw@snu.ac.kr.
FAU - Kim, Miso
AU  - Kim M
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Keam, Bhumsuk
AU  - Keam B
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Kim, Tae Min
AU  - Kim TM
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Jeon, Yoon Kyung
AU  - Jeon YK
AD  - Department of Pathology, Seoul National University Hospital, Seoul, Republic of 
      Korea. Electronic address: junarplus@chol.com.
FAU - Chung, Doo Hyun
AU  - Chung DH
AD  - Department of Pathology, Seoul National University Hospital, Seoul, Republic of 
      Korea.
FAU - Heo, Dae Seog
AU  - Heo DS
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151027
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Adenocarcinoma/*genetics/*metabolism/mortality
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Amplification
MH  - *Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*genetics/*metabolism/mortality
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Grading
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Proto-Oncogene Proteins c-met/*genetics/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Adenocarcinoma
OT  - Gene amplification
OT  - Gene expression
OT  - MET
OT  - Mutation
OT  - Non-small-cell lung carcinoma
EDAT- 2016/01/23 06:00
MHDA- 2016/10/14 06:00
CRDT- 2016/01/22 06:00
PHST- 2015/09/07 00:00 [received]
PHST- 2015/10/20 00:00 [revised]
PHST- 2015/10/22 00:00 [accepted]
PHST- 2016/01/22 06:00 [entrez]
PHST- 2016/01/23 06:00 [pubmed]
PHST- 2016/10/14 06:00 [medline]
AID - S0169-5002(15)30091-X [pii]
AID - 10.1016/j.lungcan.2015.10.022 [doi]
PST - ppublish
SO  - Lung Cancer. 2015 Dec;90(3):381-7. doi: 10.1016/j.lungcan.2015.10.022. Epub 2015 
      Oct 27.