title: Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis: clues from a study of Barrett's oesophagus.
abstract: BACKGROUND
  Human leucocyte antigen (HLA) expression is altered in oesophageal carcinomas compared with normal tissue. It is unclear, however, whether this phenotype precedes malignant transformation or results as a consequence of it.
  
  
  OBJECTIVE
  To investigate HLA class I and II expression in Barrett's oesophagus and normal squamous oesophageal tissue.
  
  
  METHODS
  Asian patients with Barrett's oesophagus (n = 64) and a control group (n = 60) with a normal oesophagus but without reflux symptoms were recruited using endoscopic and histopathological criteria. Tissue samples were stained with monoclonal antibodies specific for HLA-ABC, HLA-DR alpha chain or HLA-DP/DQ/DR, and scored semiquantitatively. The results of immunohistochemical staining were correlated with clinical and histopathological characteristics of patients.
  
  
  RESULTS
  Marked expression of HLA-ABC was observed in 50% of Barrett's oesophagus sections as compared with 68.3% of controls (p = 0.038). HLA-DR staining was seen in 51.6% of Barrett's oesophagus samples versus 11.7% of controls (p<0.001). Expression of HLA-DP/DQ/DR was evident in 73.4% of oesophageal intestinal metaplasia tissue as opposed to 18.3% of controls (p<0.001). Importantly, a total loss of HLA-ABC and a concomitant gain of HLA-DP/DQ/DR expression were seen in 37.5% of patients with Barrett's oesophagus but in none of the controls (p<0.001). Interestingly, this phenotype was associated positively with dysplasia (adjusted p, p* = 0.031) but negatively with non-steroidal anti-inflammatory drug use (p* = 0.004).
  
  
  CONCLUSIONS
  HLA class I expression is down regulated and class II expression is up regulated in Barrett's oesophagus. As these changes predate malignant transformation, altered major histocompatibility complex expression may be a key event in disease progression, possibly in facilitating evasion from immune surveillance.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Royal College of Medicine, Perak, Malaysia. shanraj@pd.jaring.my
authors.forename: S
authors.initials: S
authors.lastname: Rajendra
authors.forename: R
authors.initials: R
authors.lastname: Ackroyd
authors.forename: N
authors.initials: N
authors.lastname: Karim
authors.forename: C
authors.initials: C
authors.lastname: Mohan
authors.forename: J J
authors.initials: JJ
authors.lastname: Ho
authors.forename: M K
authors.initials: MK
authors.lastname: Kutty
mesh_terms: D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II