ORIGINAL ARTICLE

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

S Rajendra¹, R Ackroyd², N Karim³, C Mohan⁴, J J Ho⁵ and M K Kutty⁶

¹ Division of Gastroenterology, Department of Medicine, Royal College of Medicine, Perak, Malaysia
² Department of Surgery, Royal Hallamshire Hospital, Sheffield, UK
³ Department of Pathology, Ipoh Hospital, Perak
⁴ Center for Immunology, Department of Internal Medicine/Rheumatology, University of Texas Southwestern Medical Centre, Dallas, Texas, USA
⁵ Division of Epidemiology and Statistics, Department of Paediatrics, Royal College of Medicine, Ipoh, Perak
⁶ Department of Pathology, Universiti Teknologi Mara, Selangor, Malaysia

Correspondence to:
Correspondence to:
S Rajendra
Department of Medicine, Launceston General Hospital, Launceston, Tasmania 7250, Australia; shanraj{at}pd.jaring.my

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 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.

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

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