Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung.
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Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung. / Grob, Tobias; Kannengiesser, Ivonne; Tsourlakis, Maria C; Atanackovic, Djordje; König, Alexandra; Vashist, Yogesh; Klose, Hans; Marx, Andreas H; Koops, Susan; Simon, Ronald; Izbicki, Jakob R.; Bokemeyer, Carsten; Sauter, Guido; Wilczak, Waldemar.
in: MODERN PATHOL, Jahrgang 25, Nr. 12, 12, 2012, S. 1566-1573.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung.
AU - Grob, Tobias
AU - Kannengiesser, Ivonne
AU - Tsourlakis, Maria C
AU - Atanackovic, Djordje
AU - König, Alexandra
AU - Vashist, Yogesh
AU - Klose, Hans
AU - Marx, Andreas H
AU - Koops, Susan
AU - Simon, Ronald
AU - Izbicki, Jakob R.
AU - Bokemeyer, Carsten
AU - Sauter, Guido
AU - Wilczak, Waldemar
PY - 2012
Y1 - 2012
N2 - The HER2 protein, encoded by the ERBB2 gene, is a molecular target for the treatment of breast and gastric cancer by monoclonal antibodies or tyrosine kinase inhibitors. While intratumoral heterogeneity of ERBB2 amplification is rare in breast cancer it is reported to be frequent in bladder and colorectal cancer. To address the potential heterogeneity of the HER2 status in adenocarcinomas, squamous cell carcinomas and large cell undifferentiated carcinomas of the lung, 590 tumors were analyzed for HER2 overexpression and ERBB2 amplification using FDA-approved reagents for immunohistochemistry and fluorescence in-situ hybridization (FISH). Moderate and strong immunostaining (2+, 3+) was seen in 10% of the tumors. ERBB2 amplification was found in 17 (3%) lung cancer patients including 10 cases (2%) with high-level amplification forming gene clusters. ERBB2 amplification was significantly related to histologic subtype and tumor grade, resulting in 12% ERBB2 amplified tumors in the subgroup of high-grade adenocarcinomas. Heterogeneity was analyzed in all highly amplified tumors. For this purpose, all available tumor tissue blocks from these patients were evaluated. Heterogeneity of ERBB2 amplification was found in 4 of 10 tumors as assessed by FISH. These included two tumors with a mixture of low-level and high-level amplification and two tumors with non-amplified tumor areas next to regions with high-level ERBB2 amplification. High-level ERBB2 amplification occurs in a small fraction of lung cancers with a strong propensity to high-grade adenocarcinomas. Heterogeneity of amplification may limit the utility of anti-HER2 therapy in some of these tumors. Further attempts to assess the utility of HER2-targeting therapy in homogeneously amplified lung cancers appear to be justified.
AB - The HER2 protein, encoded by the ERBB2 gene, is a molecular target for the treatment of breast and gastric cancer by monoclonal antibodies or tyrosine kinase inhibitors. While intratumoral heterogeneity of ERBB2 amplification is rare in breast cancer it is reported to be frequent in bladder and colorectal cancer. To address the potential heterogeneity of the HER2 status in adenocarcinomas, squamous cell carcinomas and large cell undifferentiated carcinomas of the lung, 590 tumors were analyzed for HER2 overexpression and ERBB2 amplification using FDA-approved reagents for immunohistochemistry and fluorescence in-situ hybridization (FISH). Moderate and strong immunostaining (2+, 3+) was seen in 10% of the tumors. ERBB2 amplification was found in 17 (3%) lung cancer patients including 10 cases (2%) with high-level amplification forming gene clusters. ERBB2 amplification was significantly related to histologic subtype and tumor grade, resulting in 12% ERBB2 amplified tumors in the subgroup of high-grade adenocarcinomas. Heterogeneity was analyzed in all highly amplified tumors. For this purpose, all available tumor tissue blocks from these patients were evaluated. Heterogeneity of ERBB2 amplification was found in 4 of 10 tumors as assessed by FISH. These included two tumors with a mixture of low-level and high-level amplification and two tumors with non-amplified tumor areas next to regions with high-level ERBB2 amplification. High-level ERBB2 amplification occurs in a small fraction of lung cancers with a strong propensity to high-grade adenocarcinomas. Heterogeneity of amplification may limit the utility of anti-HER2 therapy in some of these tumors. Further attempts to assess the utility of HER2-targeting therapy in homogeneously amplified lung cancers appear to be justified.
KW - Adult
KW - Humans
KW - Aged
KW - Middle Aged
KW - Aged, 80 and over
KW - Survival Rate
KW - Kaplan-Meier Estimate
KW - In Situ Hybridization, Fluorescence
KW - Tissue Array Analysis
KW - Germany/epidemiology
KW - Gene Amplification
KW - Receptor, erbB-2/genetics
KW - Lymph Nodes/pathology
KW - Adenocarcinoma/genetics/mortality/secondary
KW - Carcinoma, Squamous Cell/genetics/mortality/secondary
KW - DNA, Neoplasm/analysis
KW - Lung Neoplasms/genetics/mortality/pathology
KW - Adult
KW - Humans
KW - Aged
KW - Middle Aged
KW - Aged, 80 and over
KW - Survival Rate
KW - Kaplan-Meier Estimate
KW - In Situ Hybridization, Fluorescence
KW - Tissue Array Analysis
KW - Germany/epidemiology
KW - Gene Amplification
KW - Receptor, erbB-2/genetics
KW - Lymph Nodes/pathology
KW - Adenocarcinoma/genetics/mortality/secondary
KW - Carcinoma, Squamous Cell/genetics/mortality/secondary
KW - DNA, Neoplasm/analysis
KW - Lung Neoplasms/genetics/mortality/pathology
M3 - SCORING: Journal article
VL - 25
SP - 1566
EP - 1573
JO - MODERN PATHOL
JF - MODERN PATHOL
SN - 0893-3952
IS - 12
M1 - 12
ER -
