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.

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@article{2e104642e1b04b5b9e06c835c3396f0e,
title = "Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer",
abstract = "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.",
keywords = "Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Gene Dosage, Humans, In Situ Hybridization, Fluorescence, Lung Neoplasms, Male, Middle Aged, Neoplasm Metastasis, Prognosis, Receptor, Epidermal Growth Factor, Tissue Array Analysis, Tumor Markers, Biological",
author = "Grob, {Tobias J} and Tobias Hoenig and Clauditz, {Till S} and Djordje Atanackovic and Koenig, {Alexandra M} and Vashist, {Yogesh K} and Hans Klose and Ronald Simon and Klaus Pantel and Izbicki, {Jakob R} and Carsten Bokemeyer and Guido Sauter and Waldemar Wilczak",
note = "Copyright {\textcopyright} 2012 Elsevier Ireland Ltd. All rights reserved.",
year = "2013",
month = mar,
day = "1",
doi = "10.1016/j.lungcan.2012.11.009",
language = "English",
volume = "79",
pages = "221--7",
journal = "LUNG CANCER",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

RIS

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 -