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.
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.
Rajendra
S
S
Division of Gastroenterology, Department of Medicine, Royal College of Medicine, Perak, Malaysia. shanraj@pd.jaring.my
Ackroyd
R
R
Karim
N
N
Mohan
C
C
Ho
J J
JJ
Kutty
M K
MK
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*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II