Expression of apoptosis regulating proteins identifies stage II and III colon cancer patients with high risk of recurrence

J Surg Oncol. 2014 Mar;109(3):255-65. doi: 10.1002/jso.23495. Epub 2013 Nov 19.

Abstract

Background and objectives: Deregulation of apoptosis related genes may be associated with poor outcome in cancer. Aim of the present study was to investigate the prognostic role of expression levels of apoptosis related proteins in stage II and III colon cancer.

Methods: From tumor samples of 386 stage II and III colon cancer patients, DNA was isolated and tissue microarrays were constructed. Expression of Bcl-2, Bcl-X, BAX, XIAP, Fas, FasL and c-FLIP was evaluated and PCR-based microsatellite instability analysis was performed.

Results: High FasL expressing tumors were associated with high disease recurrence rates in stage II colon cancer patients overall, as was low Bcl-X expression in microsatellite stable stage II patients. In stage II patients, a multivariable model based on FasL and Bcl-XL expression revealed a significant association with disease free survival (DFS). In stage III colon cancer patients, low Bcl-2, low BAX and low Fas expression levels were associated with worse outcome. In these patients a multivariable model based on angioinvasion and Bcl-2, Fas and FasL expression was significantly associated with DFS.

Conclusions: Stage II patients with low Bcl-X and high FasL protein expression levels and stage III patients with low Fas, high FasL and low Bcl-2 expression could be considered as high risk for disease recurrence.

Keywords: apoptosis; colon cancer; proteins; recurrence.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / analysis*
  • Apoptosis Regulatory Proteins / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • CASP8 and FADD-Like Apoptosis Regulating Protein / analysis
  • Colonic Neoplasms / chemistry*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • DNA, Neoplasm / metabolism
  • Disease-Free Survival
  • Fas Ligand Protein / analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Tissue Array Analysis
  • X-Linked Inhibitor of Apoptosis Protein / analysis
  • bcl-2-Associated X Protein / analysis
  • bcl-X Protein / analysis
  • fas Receptor / analysis

Substances

  • Apoptosis Regulatory Proteins
  • BAX protein, human
  • Biomarkers, Tumor
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • DNA, Neoplasm
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Proto-Oncogene Proteins c-bcl-2
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • fas Receptor