title: Discordant human epidermal growth factor receptor 2 overexpression in primary and metastatic upper gastrointestinal adenocarcinoma signifies poor prognosis.
abstract: OBJECTIVE
  Targeted therapy with trastuzumab has proved to be effective for patients with gastric cancer overexpressing the human epidermal growth factor receptor 2 (HER2). Further studies are needed to determine the best method for assessment of HER2 overexpression. Moreover, the prognostic value of HER2 overexpression, including the significance of tumour heterogeneity, remains unclear.
  
  
  RESULTS
  HER2 overexpression and gene copy alterations were assessed by immunohistochemistry and silver in-situ hybridization, respectively, on tissue microarrays with primary tumours and a subset of paired lymph node metastases from 174 patients with oesophageal or gastric adenocarcinoma. Cox proportional hazards modelling was applied to assess the prognostic impact of HER2 overexpression, intratumoural heterogeneity and conversion from primary tumour to metastasis. The correlation between protein expression and gene amplification was in line with previous studies. Primary-metastatic conversion was observed in 12.9% of the cases. HER2 overexpression or intratumoural heterogeneity was not prognostic, but primary-metastatic conversion was an independent predictor of a shorter overall survival (hazard ratio = 4.93).
  
  
  CONCLUSIONS
  As trastuzumab is emerging as an important targeted therapy for patients with upper gastointestinal cancer, these results underline the importance of further studies addressing the occurrence and clinical significance of discrepant HER2 expression in primary tumours and metastases.
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Hedner
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Tran
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Borg
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Eberhard
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2; gastric adenocarcinoma; heterogeneity; oesophageal adenocarcinoma; prognosis