title: Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer.
abstract: BACKGROUND
  National guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen.
  
  
  METHODS
  HER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed.
  
  
  RESULTS
  HER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (p < 0.001). GCs with differentiated histological features were more commonly HER2 positive (p < 0.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100 % concordance between the biopsy specimens and the resection specimen.
  
  
  CONCLUSIONS
  This is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan. takujigotoda@yahoo.co.jp.|Departments of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan. takujigotoda@yahoo.co.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tominaga
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Gotoda
authors.affiliation: Department of Preventive Medicine, Faculty of Medicine, Saga Medical School, Saga, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hara
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hale
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.|Department of Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Matsubayashi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kono
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kusano
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.affiliation: Departments of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Moriyasu
authors.affiliation: Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. heike.grabsch@mumc.nl.|Department of Pathology, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. heike.grabsch@mumc.nl.|GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. heike.grabsch@mumc.nl.
authors.forename: Heike I
authors.initials: HI
authors.lastname: Grabsch
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001706:Biopsy / Q000379:methods*; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Gastric cancer; HER2 expression; Virtual biopsy