title: Combined HER2 analysis of biopsies and surgical specimens to optimize detection of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study.
abstract: BACKGROUND
  HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DBs) and surgical specimens (SSs) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression.
  
  
  METHODS
  Pathological specimens from biopsies of 228 patients operated on between 2004 and 2011 were collected. Two cohorts treated (n = 141) or not (n = 87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were carried out using immunohistochemistry (IHC) and colorimetric in situ hybridization (CISH). HER-2 overexpression (HER2+) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, according to the specific HER2 scoring guidelines for GE-ADK.
  
  
  RESULTS
  Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2+ rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2+ tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 6% of cases. When DB analyses were added to SS analyses, the relative increase in HER2+ cases was 13.5% (17.1% for patients with NAC and 23.5% for patients with histological response to NAC, versus 7.1% for patients without NAC, P = 0.4, NS). Differences between DB and SS HER2 expression could be explained by intratumoral heterogeneity and by a HER2 expression decrease in SS after NAC in responding patients possibly due to a higher chemosensitivity of HER2-positive clones.
  
  
  CONCLUSIONS
  The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, and particularly in previously NAC-responding patients.
authors.affiliation: Department of Medical Oncology.
authors.forename: S
authors.initials: S
authors.lastname: Watson
authors.forename: P
authors.initials: P
authors.lastname: Validire
authors.forename: P
authors.initials: P
authors.lastname: Cervera
authors.forename: N
authors.initials: N
authors.lastname: Zorkani
authors.forename: A
authors.initials: A
authors.lastname: Scriva
authors.forename: F
authors.initials: F
authors.lastname: Lemay
authors.forename: C
authors.initials: C
authors.lastname: Tournigand
authors.forename: T
authors.initials: T
authors.lastname: Perniceni
authors.forename: M-L
authors.initials: ML
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Bennamoun
authors.forename: F
authors.initials: F
authors.lastname: Paye
authors.forename: C
authors.initials: C
authors.lastname: Louvet
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016037:Single-Blind Method; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Her2; gastric cancer; neoadjuvant chemotherapy