E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett oesophagus

J Clin Pathol. 2008 May;61(5):601-5. doi: 10.1136/jcp.2007.050963. Epub 2007 Oct 1.

Abstract

Background: E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (OSCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). To date there are no data regarding E2F-1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett oesophagus.

Aim: As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined the manner in which E2F-1 acts in ACs of Barrett oesophagus.

Methods: We estimated the immunohistochemical expression of E2F-1, Ki-67, caspase-3 and p53 immunohistochemical status in 35 Barrett oesophagus ACs.

Results: E2F-1 immunopositivity correlated inversely with Ki-67, by semi-serial section and statistical analysis (p = 0.023, Spearman correlation). Semi-serial section analysis revealed a direct association between E2F-1 and caspase-3 staining. No correlation was found with p53 status. Cases with higher E2F-1 immunoexpression exhibited longer survival (p = 0.047, Cox-regression).

Conclusions: E2F-1 expression was negatively related to tumour proliferation in ACs of Barrett oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient survival. These findings are opposite from those seen in OSCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett mucosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • E2F1 Transcription Factor / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Neoplasm Proteins