Heterogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer
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- 作者：Phillip Stahl ; Carsten Seeschaaf ; Patrick Lebok ; Asad Kutup…
- 关键词：HER2 ; EGFR ; MYC ; CCND1 ; Gene amplification ; Gastric cancer ; Heterogeneity tissue microarray
- 刊名：BMC Gastroenterology
- 出版年：2015
- 出版时间：December 2015
- 年：2015
- 卷：15
- 期：1
- 全文大小：1,524 KB
- 参考文献：1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137-0. rnal" href="http://dx.doi.org/10.1200/JCO.2005.05.2308" target="_blank" title="It opens in new window">CrossRef
- 刊物主题：Gastroenterology; Internal Medicine;
- 出版者：BioMed Central
- ISSN：1471-230X
文摘
Background Intra-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. Methods To 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?≥-.0). Her2 immunohistochemistry (IHC) was performed in addition. Results Amplification 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--.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 ( Conclusion The 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.