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. Rajendra, R. Ackroyd, N. Karim, C. Mohan, J. J. Ho, M. K. Kutty

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)952-957
Number of pages6
JournalJournal of Clinical Pathology
Volume59
Issue number9
DOIs
StatePublished - Sep 2006

Fingerprint

Barrett Esophagus
HLA Antigens
Carcinogenesis
Staining and Labeling
Phenotype
Immune Evasion
Metaplasia
Prednisolone
Major Histocompatibility Complex
Esophagus
Disease Progression
Anti-Inflammatory Agents
Monoclonal Antibodies
Carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. / Rajendra, S.; Ackroyd, R.; Karim, N.; Mohan, C.; Ho, J. J.; Kutty, M. K.

In: Journal of Clinical Pathology, Vol. 59, No. 9, 09.2006, p. 952-957.

Research output: Contribution to journalArticle

Rajendra, S. ; Ackroyd, R. ; Karim, N. ; Mohan, C. ; Ho, J. J. ; Kutty, M. K. / 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. In: Journal of Clinical Pathology. 2006 ; Vol. 59, No. 9. pp. 952-957.
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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.",
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T1 - Loss of human leucocyte antigen class I and gain of class II expression are early events in carcinogenesis

T2 - Clues from a study of Barrett's oesophagus

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AU - Ackroyd, R.

AU - Karim, N.

AU - Mohan, C.

AU - Ho, J. J.

AU - Kutty, M. K.

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AB - 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.

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