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PMID: 25778705 已发表 · ppublish 英语

Tumor profiling of gastric and esophageal carcinoma reveal different treatment options.

Cancer biology & therapy ·第 16 卷 ·第 5 期 ·2016-03-01

Miura John T, Xiu Joanne, Thomas James, George Ben, Carron Benjamin R, Tsai Susan, Johnston Fabian M, Turaga Kiran K, Gamblin T Clark

摘要

NCCN states that chemotherapies for advanced esophageal and gastric cancers may be used interchangeably. Biomarkers from gastroesophageal cancer patients were interrogated to identify actionable alterations with therapeutic implications.,666 gastric and 640 esophageal cancer cases referred to Caris Life Sciences between 2009 thru 2013 were evaluated. Specific testing was performed, which included a combination of sequencing (Sanger, NGS) and protein expression (IHC).,In the complete cohort (n = 1306), 30 of 45 genes tested harbored mutations; highest rates were seen in TP53 (54%), APC (10%), SMAD4 (5.9%), KRAS (5.9%), and PIK3CA (5.1%). IHC of TOP2A was high in 76% of cases, TOPO1 in 51% and SPARC in 25%; low IHC of ERCC1 was seen in 65%, RRM1 in 62%, TS in 61% and MGMT in 45%, indicating potential benefit from epirubicin, irinotecan, nab-paclitaxel, platinum-based agents, gemcitabine, 5FU/capecitabine and temozolomide, respectively. In the HER2+ cohort (n = 88), 50% of patients demonstrated possible benefit from a combination of trastuzumab with 5FU/capecitabine based on concurrent low TS, 53% with irinotecan (high TOPO1), 63% with cisplatin (low ERCC1) and 55% with gemcitabine (low RRM1). Subgroup analysis by tumor origin demonstrated significant differences in actionable biomarker profiles with HER2 (13% vs. 4.6%), SPARC (34% vs. 15%), TOP2A (86% vs. 67%), and TOPO1 (55% vs. 46%) in esophageal and gastric adenocarcinoma cases respectively (P < 0.05).,A comprehensive multiplatform biomarker analysis suggested significant biomarker differences between gastric and esophageal cancers. These results can assist in the development of future clinical trials.

关键词
EC Esophageal cancer FISH Fluorescent and chromogenic in-situ hybridization. GC Gastric cancer HER2 Human epidermal growth factor receptor 2 IHC Immunohistochemistry biomarker esophageal cancer gastric cancer molecular profiling personalized medicine
文献信息
期刊
Cancer biology & therapy
期刊简称
Cancer Biol Ther
发表日期
2016-03-01
收录日期
2015-05-22
更新日期
2016-03-16
语言
英语
国家/地区
United States
NLM ID
101137842
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