title: Combined analysis of HLA class I, HLA-E and HLA-G predicts prognosis in colon cancer patients.
abstract: BACKGROUND
  Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumour development in colon cancer. The goal of this study was to establish a tumour profile based on biomarkers that reflect a tumour's immune susceptibility status and to determine their relation to patient outcome.
  
  
  METHODS
  The study population consisted of 285 stage I-IV colon cancer patients of which a tissue micro array (TMA) was available. Sections were immunohistochemically stained for the presence of Foxp3+ cells and tumour expression of HLA Class I (HLA-A, -B, -C) and non-classical HLA-E and HLA-G. All markers were combined for further analyses, resulting in three tumour immune phenotypes: strong immune system tumour recognition, intermediate immune system tumour recognition and poor immune system tumour recognition.
  
  
  RESULTS
  Loss of HLA class I expression was significantly related to a better OS (P-value 0.005) and DFS (P-value 0.008). Patients with tumours who showed neither HLA class I nor HLA-E or -G expression (phenotype a) had a significant better OS and DFS (P-value <0.001 and 0.001, respectively) compared with phenotype b (OS HR: 4.7, 95% CI: 1.2-19.0, P=0.001) or c (OS HR: 8.2, 95% CI: 2.0-34.2, P=0.0001). Further, the tumour immune phenotype was an independent predictor for OS and DFS (P-value 0.009 and 0.013, respectively).
  
  
  CONCLUSIONS
  Tumours showing absence of HLA class I, HLA-E and HLA-G expressions were related to a better OS and DFS. By combining the expression status of several immune-related biomarkers, three tumour immune phenotypes were created that related to patient outcome. These immune phenotypes represented significant, independent, clinical prognostic profiles in colon cancer.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: E C M
authors.initials: EC
authors.lastname: Zeestraten
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: M S
authors.initials: MS
authors.lastname: Reimers
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Saadatmand
authors.forename: Inès J
authors.initials: IJ
authors.lastname: Goossens-Beumer
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: J-W T
authors.initials: JW
authors.lastname: Dekker
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.affiliation: 1] Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands [2] Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: van den Elsen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I / Q000276:immunology*; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000097625:HLA-E Antigens
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens; C418974:FOXP3 protein, human