title: Clinical impact of HLA class I expression in rectal cancer.
abstract: OBJECTIVE
  To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas.
  
  
  METHODS
  Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10).
  
  
  RESULTS
  Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival.
  
  
  CONCLUSIONS
  Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed.
authors.affiliation: Department of Surgery, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. f.m.speetjens@lumc.nl
authors.forename: Frank M
authors.initials: FM
authors.lastname: Speetjens
authors.forename: Elza C
authors.initials: EC
authors.lastname: de Bruin
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Eliane C M
authors.initials: EC
authors.lastname: Zeestraten
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: J Han
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Maaike M
authors.initials: MM
authors.lastname: van Buren
authors.forename: Monique
authors.initials: M
authors.lastname: van Velzen
authors.forename: N Geeske
authors.initials: NG
authors.lastname: Dekker-Ensink
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053842:Microsatellite Instability; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I