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Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer

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Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer. / Stahl, Phillip; Seeschaaf, Carsten; Lebok, Patrick; Kutup, Asad; Bockhorn, Maximilian; Izbicki, Jakob R; Bokemeyer, Carsten; Simon, Ronald; Sauter, Guido; Marx, Andreas H.

In: BMC GASTROENTEROL, Vol. 15, No. 1, 05.02.2015, p. 7.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Stahl, P, Seeschaaf, C, Lebok, P, Kutup, A, Bockhorn, M, Izbicki, JR, Bokemeyer, C, Simon, R, Sauter, G & Marx, AH 2015, 'Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer', BMC GASTROENTEROL, vol. 15, no. 1, pp. 7. https://doi.org/10.1186/s12876-015-0231-4

APA

Stahl, P., Seeschaaf, C., Lebok, P., Kutup, A., Bockhorn, M., Izbicki, J. R., Bokemeyer, C., Simon, R., Sauter, G., & Marx, A. H. (2015). Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer. BMC GASTROENTEROL, 15(1), 7. https://doi.org/10.1186/s12876-015-0231-4

Vancouver

Stahl P, Seeschaaf C, Lebok P, Kutup A, Bockhorn M, Izbicki JR et al. Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer. BMC GASTROENTEROL. 2015 Feb 5;15(1):7. https://doi.org/10.1186/s12876-015-0231-4

Bibtex

@article{9c27d8dce0c9441997fe14b19cff0026,
title = "Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer",
abstract = "BackgroundIntra-tumor heterogeneity is a potential cause for failure of targeted therapy in gastric cancer, but the extent of heterogeneity of established (HER2) or potential (EGFR, CCND1) target genes and prognostic gene alterations (MYC) had not been systematically studied.MethodsTo study heterogeneity of these genes in a large patient cohort, a heterogeneity tissue microarray was constructed containing 0.6 mm tissue cores from 9 different areas of the primary gastric cancers of 113 patients and matched lymph node metastases from 61 of these patients. Dual color fluorescence in-situ hybridization was performed to assess amplification of HER2, EGFR, CCND1 and MYC using established thresholds (ratio¿¿¿2.0). Her2 immunohistochemistry (IHC) was performed in addition.ResultsAmplification was found in 17.4% of 109 interpretable cases for HER2, 6.4% for EGFR, 17.4% for CCND1, and 24.8% for MYC. HER2 amplification was strongly linked to protein overexpression by IHC in a spot-by-spot analysis (p¿<¿0.0001). Intra-tumor heterogeneity was found in the primary tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.2%) cancers with MYC amplification. Amplification heterogeneity was particularly frequent in case of low-level amplification (<10 gene copies). While the amplification status was often different between metastases, unequivocal intra-tumor heterogeneity was not found in individual metastases.ConclusionThe data of our study demonstrate that heterogeneity is common for biomarkers in gastric cancer. Given that both TMA tissue cores and clinical tumor biopsies analyze only a small fraction of the tumor bulk, it can be concluded that such heterogeneity may potentially limit treatment decisions based on the analysis of a single clinical cancer biopsy.",
author = "Phillip Stahl and Carsten Seeschaaf and Patrick Lebok and Asad Kutup and Maximilian Bockhorn and Izbicki, {Jakob R} and Carsten Bokemeyer and Ronald Simon and Guido Sauter and Marx, {Andreas H}",
year = "2015",
month = feb,
day = "5",
doi = "10.1186/s12876-015-0231-4",
language = "English",
volume = "15",
pages = "7",
journal = "BMC GASTROENTEROL",
issn = "1471-230X",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer

AU - Stahl, Phillip

AU - Seeschaaf, Carsten

AU - Lebok, Patrick

AU - Kutup, Asad

AU - Bockhorn, Maximilian

AU - Izbicki, Jakob R

AU - Bokemeyer, Carsten

AU - Simon, Ronald

AU - Sauter, Guido

AU - Marx, Andreas H

PY - 2015/2/5

Y1 - 2015/2/5

N2 - BackgroundIntra-tumor heterogeneity is a potential cause for failure of targeted therapy in gastric cancer, but the extent of heterogeneity of established (HER2) or potential (EGFR, CCND1) target genes and prognostic gene alterations (MYC) had not been systematically studied.MethodsTo study heterogeneity of these genes in a large patient cohort, a heterogeneity tissue microarray was constructed containing 0.6 mm tissue cores from 9 different areas of the primary gastric cancers of 113 patients and matched lymph node metastases from 61 of these patients. Dual color fluorescence in-situ hybridization was performed to assess amplification of HER2, EGFR, CCND1 and MYC using established thresholds (ratio¿¿¿2.0). Her2 immunohistochemistry (IHC) was performed in addition.ResultsAmplification was found in 17.4% of 109 interpretable cases for HER2, 6.4% for EGFR, 17.4% for CCND1, and 24.8% for MYC. HER2 amplification was strongly linked to protein overexpression by IHC in a spot-by-spot analysis (p¿<¿0.0001). Intra-tumor heterogeneity was found in the primary tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.2%) cancers with MYC amplification. Amplification heterogeneity was particularly frequent in case of low-level amplification (<10 gene copies). While the amplification status was often different between metastases, unequivocal intra-tumor heterogeneity was not found in individual metastases.ConclusionThe data of our study demonstrate that heterogeneity is common for biomarkers in gastric cancer. Given that both TMA tissue cores and clinical tumor biopsies analyze only a small fraction of the tumor bulk, it can be concluded that such heterogeneity may potentially limit treatment decisions based on the analysis of a single clinical cancer biopsy.

AB - BackgroundIntra-tumor heterogeneity is a potential cause for failure of targeted therapy in gastric cancer, but the extent of heterogeneity of established (HER2) or potential (EGFR, CCND1) target genes and prognostic gene alterations (MYC) had not been systematically studied.MethodsTo study heterogeneity of these genes in a large patient cohort, a heterogeneity tissue microarray was constructed containing 0.6 mm tissue cores from 9 different areas of the primary gastric cancers of 113 patients and matched lymph node metastases from 61 of these patients. Dual color fluorescence in-situ hybridization was performed to assess amplification of HER2, EGFR, CCND1 and MYC using established thresholds (ratio¿¿¿2.0). Her2 immunohistochemistry (IHC) was performed in addition.ResultsAmplification was found in 17.4% of 109 interpretable cases for HER2, 6.4% for EGFR, 17.4% for CCND1, and 24.8% for MYC. HER2 amplification was strongly linked to protein overexpression by IHC in a spot-by-spot analysis (p¿<¿0.0001). Intra-tumor heterogeneity was found in the primary tumors of 9 of 19 (47.3%) cancers with HER2, 8 of 17 (47.0%) cancers with CCND1, 5 of 7 (71.4%) cancers with EGFR, and 23 of 27 (85.2%) cancers with MYC amplification. Amplification heterogeneity was particularly frequent in case of low-level amplification (<10 gene copies). While the amplification status was often different between metastases, unequivocal intra-tumor heterogeneity was not found in individual metastases.ConclusionThe data of our study demonstrate that heterogeneity is common for biomarkers in gastric cancer. Given that both TMA tissue cores and clinical tumor biopsies analyze only a small fraction of the tumor bulk, it can be concluded that such heterogeneity may potentially limit treatment decisions based on the analysis of a single clinical cancer biopsy.

U2 - 10.1186/s12876-015-0231-4

DO - 10.1186/s12876-015-0231-4

M3 - SCORING: Journal article

C2 - 25649416

VL - 15

SP - 7

JO - BMC GASTROENTEROL

JF - BMC GASTROENTEROL

SN - 1471-230X

IS - 1

ER -