title: Upfront molecular testing in patients with advanced gastro-esophageal cancer: Is it time yet?
abstract: BACKGROUND
  Targeting HER2 has improved outcomes in metastatic GE (mGE) cancer. In this study, we aim to explore the feasibility of molecular profiling in patients with refractory mGE cancer in routine clinical practice.
  
  
  METHODS
  Archival formalin-fixed, paraffin-embedded (FFPE) samples for patients with mGE were analyzed with commercially available targeted next generation sequencing (NGS) and/or FISH for MET amplification. We also reviewed the patients' medical records for concurrent HER 2 testing.
  
  
  RESULTS
  Tumor samples from 99 patients with mGE cancer were analyzed as follows: NGS (N = 56), FISH for MET amplification (N = 65), IHC and/or FISH for HER2 (N = 87). Of patients who underwent NGS, 50/56 (89%) had at least one actionable molecular alteration. The most notable actionable alterations included cell cycle abnormalities (58%), HER2 amplification (30%), PI3KCA mutation (14%), MCL1 amplification (11%), PTEN loss (9%), CDH1 mutation (2%) and MET amplification (5%). Ninety-two percent (12/13) of patients with HER2 amplification by NGS were positive for HER2 by IHC and/or FISH. In contrast, only 12/18 (66%) patients positive for HER2 by IHC and/or FISH demonstrated HER2 amplification by NGS.
  
  
  CONCLUSIONS
  Comprehensive molecular testing is feasible in clinical practice and provides a platform for screening patients for molecularly guided clinical trials and available targeted therapies.
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Sameh
authors.initials: S
authors.lastname: Mikhail
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Ciombor
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Noonan
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Goldberg
authors.affiliation: Department of Pathology, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Biostatistics, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Mathey
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Yereb
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Timmers
authors.affiliation: Department of Medicine, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio 43221, USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C491743:MET protein, human
keywords: c-MET; gastro-esophageal cancer; molecular profiling; next generation sequencing; targeted therapy