title: Expression of apoptosis regulating proteins identifies stage II and III colon cancer patients with high risk of recurrence.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Eric J Th
authors.initials: EJ
authors.lastname: Belt
authors.forename: Hein B A C
authors.initials: HB
authors.lastname: Stockmann
authors.forename: Pien M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.forename: Herman
authors.initials: H
authors.lastname: Bril
authors.forename: Marianne
authors.initials: M
authors.lastname: Tijssen
authors.forename: Hendrik F
authors.initials: HF
authors.lastname: van Essen
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.forename: Jeroen A M
authors.initials: JA
authors.lastname: Beliën
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.forename: Saskia A G M
authors.initials: SA
authors.lastname: Cillessen
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000032:analysis; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D053222:Fas Ligand Protein / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D046888:Tissue Array Analysis; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051020:bcl-X Protein / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D004273:DNA, Neoplasm; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor
keywords: apoptosis; colon cancer; proteins; recurrence