PMID- 23238037
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20181202
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 79
IP  - 3
DP  - 2013 Mar
TI  - Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung 
      cancer.
PG  - 221-7
LID - S0169-5002(12)00630-7 [pii]
LID - 10.1016/j.lungcan.2012.11.009 [doi]
AB  - Next to EGFR mutation, EGFR gene copy number evaluated by fluorescence in situ 
      hybridization (FISH) emerged as a potential predictive marker for sensitivity to 
      EGFR tyrosine kinase inhibitors, although controversial data exist. As the 
      diagnostic accuracy of predictive biomarkers can be substantially limited by 
      regional differences within tumors, heterogeneity of EGFR gene copy gain in NSCLC 
      was assessed in this study. For this purpose, a novel tissue microarray (TMA) 
      based analysis platform was developed. TMAs were constructed containing 8 
      different tissue cylinders from 144 primary NSCLCs. From 62 of these patients 
      additional nodal metastases were sampled. EGFR gene copy number and EGFR 
      expression was analyzed by FISH and immunohistochemistry according to the 
      suggested guidelines. 13 (9.0%) of the 144 evaluated tumors showed EGFR 
      amplification and 37 (25.7%) tumors high polysomy in at least one tumor area. In 
      7 (53.8%) of 13 amplified cases the analysis of different tumor areas revealed 
      subclones without EGFR gene copy gain next to subclones with amplification. All 
      of the 36 evaluable tumors with high polysomy showed heterogeneity of EGFR gene 
      copy number with areas negative for gene copy gain within the individual tumors. 
      Heterogeneity of EGFR gene copy gain in lung cancer challenges the concept of 
      using small biopsies for the analysis of EGFR FISH status. EGFR gene copy number 
      is highly heterogeneous within individual NSCLCs and this finding might well be a 
      reason for the controversial clinical data existing regarding responsiveness to 
      anti-EGFR therapy.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Grob, Tobias J
AU  - Grob TJ
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany. t.grob@uke.de
FAU - Hoenig, Tobias
AU  - Hoenig T
FAU - Clauditz, Till S
AU  - Clauditz TS
FAU - Atanackovic, Djordje
AU  - Atanackovic D
FAU - Koenig, Alexandra M
AU  - Koenig AM
FAU - Vashist, Yogesh K
AU  - Vashist YK
FAU - Klose, Hans
AU  - Klose H
FAU - Simon, Ronald
AU  - Simon R
FAU - Pantel, Klaus
AU  - Pantel K
FAU - Izbicki, Jakob R
AU  - Izbicki JR
FAU - Bokemeyer, Carsten
AU  - Bokemeyer C
FAU - Sauter, Guido
AU  - Sauter G
FAU - Wilczak, Waldemar
AU  - Wilczak W
LA  - eng
PT  - Journal Article
DEP - 20121210
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/therapy
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Gene Dosage/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*diagnosis/genetics/therapy
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Prognosis
MH  - Tissue Array Analysis
EDAT- 2012/12/15 06:00
MHDA- 2013/07/20 06:00
CRDT- 2012/12/15 06:00
PHST- 2012/04/23 00:00 [received]
PHST- 2012/11/08 00:00 [revised]
PHST- 2012/11/11 00:00 [accepted]
PHST- 2012/12/15 06:00 [entrez]
PHST- 2012/12/15 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
AID - S0169-5002(12)00630-7 [pii]
AID - 10.1016/j.lungcan.2012.11.009 [doi]
PST - ppublish
SO  - Lung Cancer. 2013 Mar;79(3):221-7. doi: 10.1016/j.lungcan.2012.11.009. Epub 2012 
      Dec 10.