title: Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer.
abstract: OBJECTIVE
  Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.
  
  
  OBJECTIVE
  To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.
  
  
  METHODS
  A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.
  
  
  METHODS
  Overall survival.
  
  
  RESULTS
  The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).
  
  
  CONCLUSIONS
  Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marlies S
authors.initials: MS
authors.lastname: Reimers
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands2Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: Medical Research Council Clinical Trials Unit, University College, London, England.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Langley
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Eijk
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ronald L P
authors.initials: RL
authors.lastname: van Vlierberghe
authors.affiliation: Comprehensive Cancer Centre South, Eindhoven Cancer Registry, Eindhoven, the Netherlands.
authors.forename: Valery E P
authors.initials: VE
authors.lastname: Lemmens
authors.affiliation: PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands.
authors.forename: Myrthe P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Experimental Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis*; D016133:Polymerase Chain Reaction; D012042:Registries; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D001241:Aspirin