TOPOIIalpha and HER-2/neu overexpression/amplification in Barrett's oesophagus, dysplasia and adenocarcinoma

Histopathology. 2010 Jul;57(1):81-9. doi: 10.1111/j.1365-2559.2010.03580.x. Epub 2010 Jun 16.

Abstract

Aims: Topoisomerase IIalpha (TOPOIIalpha) and HER-2/neu are chromosome 17q genes coamplified in various cancers; no data exist for Barrett's oesophagus (BO) and BO adenocarcinoma (ADC). The aim was to investigate gene amplification and protein overexpression of TopoIIalpha and Her-2/neu in non-dysplastic BO, dysplastic BO, Barrett ADC, and chromosome 17 aneusomy.

Methods and results: Forty-four patients [18 BO, 13 BO with dysplasia (five low-grade dysplasia, eight high-grade dysplasia) and 13 ADC in BO] were evaluated by immunohistochemistry and fluorescence in situ hybridization (FISH). Genes (HER-2/neu and TOPOIIalpha) and chromosome 17 were evaluated by FISH. Patients with BO, dysplasia and ADC were compared. A significant association was found between TOPOIIalpha protein overexpression and TopoIIalpha gene amplification, chromosome 17 aneusomy, HER-2/neu gene amplification and HER-2 protein overexpression as well as between HER-2 protein and HER-2/neu gene, TopoIIalpha gene and aneusomy for chromosome17, and between the genes TOPOIIalpha and HER-2/neu. Gene amplification (HER-2/neu, TOPOIIalpha), protein overexpression (HER-2/TOPOIIalpha), and chromosome 17 aneusomy were associated with dysplasia or ADC. Most BO patients showed no amplification/overexpression/aneusomy for the above genes, proteins and chromosome, with no differences between dysplasia and ADC.

Conclusions: HER-2/neu and TOPOIIalpha amplification/overexpression might discriminate between BO and dysplasia/ADC. Chromosome 17 aneusomy is associated with dysplasia or ADC in BO.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Barrett Esophagus / diagnosis
  • Barrett Esophagus / genetics*
  • Barrett Esophagus / metabolism
  • Barrett Esophagus / pathology*
  • Chromosomes, Human, Pair 17 / genetics
  • DNA Topoisomerases, Type II / genetics*
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Diagnosis, Differential
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Female
  • Gene Amplification
  • Gene Expression
  • Genes, erbB-2*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II