Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer
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Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer. / Grob, Tobias J; Hoenig, Tobias; Clauditz, Till S; Atanackovic, Djordje; Koenig, Alexandra M; Vashist, Yogesh K; Klose, Hans; Simon, Ronald; Pantel, Klaus; Izbicki, Jakob R; Bokemeyer, Carsten; Sauter, Guido; Wilczak, Waldemar.
In: LUNG CANCER, Vol. 79, No. 3, 01.03.2013, p. 221-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer
AU - Grob, Tobias J
AU - Hoenig, Tobias
AU - Clauditz, Till S
AU - Atanackovic, Djordje
AU - Koenig, Alexandra M
AU - Vashist, Yogesh K
AU - Klose, Hans
AU - Simon, Ronald
AU - Pantel, Klaus
AU - Izbicki, Jakob R
AU - Bokemeyer, Carsten
AU - Sauter, Guido
AU - Wilczak, Waldemar
N1 - Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Non-Small-Cell Lung
KW - Female
KW - Gene Dosage
KW - Humans
KW - In Situ Hybridization, Fluorescence
KW - Lung Neoplasms
KW - Male
KW - Middle Aged
KW - Neoplasm Metastasis
KW - Prognosis
KW - Receptor, Epidermal Growth Factor
KW - Tissue Array Analysis
KW - Tumor Markers, Biological
U2 - 10.1016/j.lungcan.2012.11.009
DO - 10.1016/j.lungcan.2012.11.009
M3 - SCORING: Journal article
C2 - 23238037
VL - 79
SP - 221
EP - 227
JO - LUNG CANCER
JF - LUNG CANCER
SN - 0169-5002
IS - 3
ER -