PMID- 23426935
OWN - NLM
STAT- MEDLINE
DCOM- 20130819
LR  - 20211021
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 42
IP  - 4
DP  - 2013 Apr
TI  - Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell 
      carcinoma.
PG  - 1151-8
LID - 10.3892/ijo.2013.1830 [doi]
AB  - Molecular targeted therapy is expected to be a promising therapeutic approach for 
      the treatment of esophageal squamous cell carcinoma (ESCC); however, the gene 
      amplification status of molecular targeted genes in ESCC remains largely unclear. 
      The gene amplification of EGFR, HER2, FGFR2 and MET was examined using a 
      real-time PCR-based copy number assay of 245 ESCC surgical specimens of 
      formalin-fixed, paraffin-embedded samples. Fluorescence in situ hybridization 
      (FISH) and comparative genomic hybridization analyses verified the results of the 
      copy number assay. EGFR mutation was detected using the Scorpions-ARMS method. 
      The EGFR status and drug sensitivity to an EGFR tyrosine kinase inhibitor was 
      then evaluated in vitro. Gene amplification of EGFR and HER2 was observed in 7% 
      (16/244) and 11% (27/245) of the ESCC specimens. A multivariate analysis revealed 
      that HER2 amplification was a significant predictor of a poor prognosis in 
      patients with stage III post-operative ESCC. The L861Q type of EGFR mutation with 
      hypersensitivity to EGFR tyrosine kinase inhibitor was found in one of the eight 
      ESCC cell lines and one del745 type of EGFR mutation was identified in 107 
      clinical samples. In addition, we demonstrated for the first time that FGFR2 
      amplification was observed in 4% (8/196) of the ESCC specimens. MET amplification 
      was observed in 1% (2/196). In conclusion, the frequent gene amplification of 
      EGFR, HER2 and FGFR2 and the presence of active EGFR mutations were observed in 
      ESCC specimens. Our results strongly encourage the development of molecular 
      targeted therapy for ESCC.
FAU - Kato, Hiroaki
AU  - Kato H
AD  - Department of Surgery, Kinki University Faculty of Medicine, Osaka 589-8511, 
      Japan. knishio@med.kindai.ac.jp
FAU - Arao, Tokuzo
AU  - Arao T
FAU - Matsumoto, Kazuko
AU  - Matsumoto K
FAU - Fujita, Yoshihiko
AU  - Fujita Y
FAU - Kimura, Hideharu
AU  - Kimura H
FAU - Hayashi, Hidetoshi
AU  - Hayashi H
FAU - Nishiki, Kouhei
AU  - Nishiki K
FAU - Iwama, Mitsuru
AU  - Iwama M
FAU - Shiraishi, Osamu
AU  - Shiraishi O
FAU - Yasuda, Atsushi
AU  - Yasuda A
FAU - Shinkai, Masayuki
AU  - Shinkai M
FAU - Imano, Motohiro
AU  - Imano M
FAU - Imamoto, Haruhiko
AU  - Imamoto H
FAU - Yasuda, Takushi
AU  - Yasuda T
FAU - Okuno, Kiyotaka
AU  - Okuno K
FAU - Shiozaki, Hitoshi
AU  - Shiozaki H
FAU - Nishio, Kazuto
AU  - Nishio K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130219
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (FGFR2 protein, human)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Cell Line, Tumor
MH  - ErbB Receptors/*genetics
MH  - Esophageal Neoplasms/*genetics
MH  - Esophageal Squamous Cell Carcinoma
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Genetic Association Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Mutation, Missense
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Receptor, ErbB-2/*genetics
MH  - Receptor, Fibroblast Growth Factor, Type 2/*genetics
PMC - PMC3622677
EDAT- 2013/02/22 06:00
MHDA- 2013/08/21 06:00
PMCR- 2013/02/19
CRDT- 2013/02/22 06:00
PHST- 2012/07/30 00:00 [received]
PHST- 2012/09/28 00:00 [accepted]
PHST- 2013/02/22 06:00 [entrez]
PHST- 2013/02/22 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
PHST- 2013/02/19 00:00 [pmc-release]
AID - ijo-42-04-1151 [pii]
AID - 10.3892/ijo.2013.1830 [doi]
PST - ppublish
SO  - Int J Oncol. 2013 Apr;42(4):1151-8. doi: 10.3892/ijo.2013.1830. Epub 2013 Feb 19.