title: Tumor profiling of gastric and esophageal carcinoma reveal different treatment options.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Division of Surgical Oncology; Medical College of Wisconsin ; Milwaukee , WI USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Miura
authors.forename: Joanne
authors.initials: J
authors.lastname: Xiu
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.forename: Ben
authors.initials: B
authors.lastname: George
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Carron
authors.forename: Susan
authors.initials: S
authors.lastname: Tsai
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Johnston
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Turaga
authors.forename: T Clark
authors.initials: TC
authors.lastname: Gamblin
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
keywords: 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