PMID- 19247083
OWN - NLM
STAT- MEDLINE
DCOM- 20090616
LR  - 20211020
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Print)
IS  - 1556-0864 (Linking)
VI  - 4
IP  - 3
DP  - 2009 Mar
TI  - EGFR and HER2 genomic gain in recurrent non-small cell lung cancer after surgery: 
      impact on outcome to treatment with gefitinib and association with EGFR and KRAS 
      mutations in a Japanese cohort.
PG  - 318-25
LID - 10.1097/JTO.0b013e31819667a3 [doi]
AB  - BACKGROUND: Sensitivity to epidermal growth factor receptor (EGFR) tyrosine 
      kinase inhibitors (TKIs) and frequency of activation mutations in EGFR is lower 
      in Caucasian than Asian non small-cell lung cancer (NSCLC) patients. Increased 
      EGFR gene copy numbers evaluated by fluorescence in situ hybridization (FISH) has 
      been reported as predictor of clinical benefit from EGFR-TKIs in Caucasian NSCLC 
      patients. This study was carried out to verify whether EGFR FISH had similar 
      performance in Japanese patients. METHODS: A cohort of 44 Japanese patients with 
      recurrent NSCLC after surgery was treated with gefitinib 250 mg daily. The cohort 
      included 48% females and 52% never-smokers; 73% had prior chemotherapy and 57% 
      had stage III-IV at the time of surgery. Adenocarcinoma was the most common 
      histology (86%). FISH was performed using the EGFR/Chromosome Enumeration Probe 7 
      and PathVysion DNA probes (Abbott Molecular). Specimens were classified as FISH 
      positive when showing gene amplification or high polysomy (> or = 4 copies of the 
      gene in > or = 40% of tumor cells). Tumor response to gefitinib was assessed by 
      RECIST for 33 patients with measurable diseases. RESULTS: Twenty-nine tumors 
      (66%) were EGFR FISH+ and 23 (53%) were HER2 FISH+. Overall response rate was 
      52%, representing 65% of EGFR FISH+ patients and 29% of EGFR FISH- patients (p = 
      0.0777). Survival was not impacted by the EGFR FISH (p = 0.9395) or the HER2 FISH 
      (p = 0.0671) status. EGFR FISH+ was significantly associated with HER2 FISH+ (p = 
      0.015) and presence of EGFR mutation (p = 0.0060). EGFR mutation significantly 
      correlated with response (p < 0.0001) and survival after gefitinib (p = 0.0204). 
      EGFR and HER2 FISH status were not associated with KRAS mutation. CONCLUSION: 
      Frequency of EGFR FISH+ status was higher and its predictive power for TKI 
      sensitivity was lower in this Japanese cohort than in Western NSCLC cohorts. 
      These findings support differences in the mechanisms of EGFR pathway activation 
      in NSCLC between Asian and Caucasian populations. Confirmation of these results 
      in larger cohorts is warranted.
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
AD  - University of Colorado Cancer Center, Department of Medicine and Pathology, 
      Aurora, CO 80045, USA.
FAU - Mitsudomi, Tetsuya
AU  - Mitsudomi T
FAU - Yatabe, Yashushi
AU  - Yatabe Y
FAU - Kosaka, Takayuki
AU  - Kosaka T
FAU - Nakajima, Eiji
AU  - Nakajima E
FAU - Xavier, Ana Carolina
AU  - Xavier AC
FAU - Skokan, Margaret
AU  - Skokan M
FAU - Zeng, Chan
AU  - Zeng C
FAU - Franklin, Wilbur A
AU  - Franklin WA
FAU - Bunn, Paul A Jr
AU  - Bunn PA Jr
FAU - Hirsch, Fred R
AU  - Hirsch FR
LA  - eng
GR  - P50 CA058187/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology/surgery
MH  - Cohort Studies
MH  - ErbB Receptors/genetics/*metabolism
MH  - Female
MH  - Gefitinib
MH  - Genes, erbB-2
MH  - *Genes, ras
MH  - Genome
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Japan
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*genetics/mortality/pathology/surgery
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Recurrence, Local/*drug therapy/*genetics/mortality/pathology
MH  - Probability
MH  - Prognosis
MH  - Quinazolines/*therapeutic use
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Statistics, Nonparametric
MH  - Survival Analysis
PMC - PMC3379811
MID - NIHMS377989
EDAT- 2009/02/28 09:00
MHDA- 2009/06/17 09:00
PMCR- 2012/06/20
CRDT- 2009/02/28 09:00
PHST- 2009/02/28 09:00 [entrez]
PHST- 2009/02/28 09:00 [pubmed]
PHST- 2009/06/17 09:00 [medline]
PHST- 2012/06/20 00:00 [pmc-release]
AID - S1556-0864(15)30983-7 [pii]
AID - 10.1097/JTO.0b013e31819667a3 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2009 Mar;4(3):318-25. doi: 10.1097/JTO.0b013e31819667a3.