PMID- 21872356
OWN - NLM
STAT- MEDLINE
DCOM- 20120424
LR  - 20190221
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 75
IP  - 2
DP  - 2012 Feb
TI  - Abnormality of the hepatocyte growth factor/MET pathway in pulmonary 
      adenocarcinogenesis.
PG  - 181-8
LID - 10.1016/j.lungcan.2011.07.008 [doi]
AB  - BACKGROUND: Signaling mediated by hepatocyte growth factor (HGF)/MET promotes 
      multiple biological activities, including cell proliferation, motility, invasion, 
      angiogenesis, and morphogenesis. Overexpression of HGF and MET and an increase of 
      the MET gene copy number have recently been found in various cancers that had a 
      poor outcome. Here we investigated the copy number of the MET gene and expression 
      of MET and HGF in small pulmonary adenocarcinomas. METHODS: Tumor tissues were 
      obtained from 106 pulmonary small adenocarcinomas 2 cm or less in diameter. MET 
      gene copy number, and the expression of MET and HGF, were analyzed using 
      fluorescence in situ hybridization (FISH) and immunohistochemistry, respectively. 
      RESULTS: MET FISH-positive signals were observed in 11 (10.4%) of 106 cases. One 
      case (0.9%) showed gene amplification and 10 (9.4%) exhibited high polysomy. High 
      immunoreactivity for MET and HGF in tumor cells was found in 30 (28.3%) and 19 
      cases (17.9%), respectively. HGF was also expressed in stromal cells in 32 cases 
      (30.2%). No cases of non-invasive adenocarcinoma (adenocarcinoma in situ, 
      localized bronchioloalveolar carcinoma) showed MET FISH-positive signals or high 
      expression of HGF in the tumor cells. Expression of both MET and stromal HGF was 
      stronger in invasive than in non-invasive adenocarcinoma. MET FISH-positive 
      signals and high immunoreactivity for MET and HGF in tumor cells were associated 
      with factors indicative of poor prognosis such as pleural invasion, vascular 
      invasion, lymphatic permeation, lymph node metastasis, and nuclear grading. 
      Univariate and multivariate analyses that included these factors showed that all 
      statuses except for MET and HGF immunoreactivity were significantly associated 
      with an increased risk of death. However, multivariate analysis revealed no 
      independent factors related to poor prognosis. CONCLUSION: Our results suggest 
      that abnormality of the HGF/MET pathway occurs during the course of progression 
      from non-invasive to invasive pulmonary adenocarcinoma. An increased MET gene 
      copy number is indicative of a poor outcome in patients with small pulmonary 
      adenocarcinomas.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Tachibana, Keisei
AU  - Tachibana K
AD  - Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 
      Shinkawa, Mitaka, Tokyo 181-8611, Japan.
FAU - Minami, Yuko
AU  - Minami Y
FAU - Shiba-Ishii, Aya
AU  - Shiba-Ishii A
FAU - Kano, Junko
AU  - Kano J
FAU - Nakazato, Yoshimasa
AU  - Nakazato Y
FAU - Sato, Yukio
AU  - Sato Y
FAU - Goya, Tomoyuki
AU  - Goya T
FAU - Noguchi, Masayuki
AU  - Noguchi M
LA  - eng
PT  - Journal Article
DEP - 20110827
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (HGF protein, human)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Adenocarcinoma/*etiology/mortality
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Hepatocyte Growth Factor/analysis/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*etiology/mortality
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-met/analysis/genetics/*physiology
MH  - Signal Transduction/*physiology
EDAT- 2011/08/30 06:00
MHDA- 2012/04/25 06:00
CRDT- 2011/08/30 06:00
PHST- 2011/02/12 00:00 [received]
PHST- 2011/06/22 00:00 [revised]
PHST- 2011/07/13 00:00 [accepted]
PHST- 2011/08/30 06:00 [entrez]
PHST- 2011/08/30 06:00 [pubmed]
PHST- 2012/04/25 06:00 [medline]
AID - S0169-5002(11)00382-5 [pii]
AID - 10.1016/j.lungcan.2011.07.008 [doi]
PST - ppublish
SO  - Lung Cancer. 2012 Feb;75(2):181-8. doi: 10.1016/j.lungcan.2011.07.008. Epub 2011 
      Aug 27.