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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
  1. S Rajendra1,
  2. R Ackroyd2,
  3. N Karim3,
  4. C Mohan4,
  5. J J Ho5,
  6. M K Kutty6
  1. 1Division of Gastroenterology, Department of Medicine, Royal College of Medicine, Perak, Malaysia
  2. 2Department of Surgery, Royal Hallamshire Hospital, Sheffield, UK
  3. 3Department of Pathology, Ipoh Hospital, Perak
  4. 4Center for Immunology, Department of Internal Medicine/Rheumatology, University of Texas Southwestern Medical Centre, Dallas, Texas, USA
  5. 5Division of Epidemiology and Statistics, Department of Paediatrics, Royal College of Medicine, Ipoh, Perak
  6. 6Department of Pathology, Universiti Teknologi Mara, Selangor, Malaysia
  1. Correspondence to:
    S Rajendra
    Department of Medicine, Launceston General Hospital, Launceston, Tasmania 7250, Australia; shanraj{at}pd.jaring.my

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.

Aim: 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 α 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.

  • HLA, human leucocyte antigen
  • MHC, major histocompatibility complex
  • NSAID, non-steroidal anti-inflammatory drug
  • TBS, Tris-buffered saline

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Footnotes

  • Competing interests: None declared.

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