High-grade dysplasia in Barrett's esophagus is associated with increased expression of calgranulin A and B.
OBJECTIVE
Patients with Barrett's esophagus (BE) are at risk of developing esophageal adenocarcinoma, which is usually preceded by dysplastic changes of the metaplastic mucosa. The aim of this study was to increase the understanding of the development of dysplastic lesions in BE through the identification of genes that are differentially transcribed in these tissue types.


METHODS
Paired biopsy samples from non-dysplastic BE, and high-grade dysplasia from a single patient were used for histological evaluation and gene expression profile analysis. In addition, relative mRNA levels of differentially expressed genes were tested to validate the association with the presence or absence of dysplasia by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) (58 biopsy samples containing squamous epithelium, non-dysplastic BE, high-grade dysplasia, or adenocarcinoma from 23 unrelated patients) and immunohistochemistry (9 sets of paired non-dysplastic/high-grade dysplasiac samples from 9 unrelated patients).


RESULTS
Microarray results from high-grade dysplasia showed 866 genes with a>2-fold difference in mRNA levels compared with non-dysplastic BE. Subsequent comparison of mRNA levels of the 22 genes with a>10-fold difference in 76 unrelated biopsies showed that only two of these genes, i.e. calgranulin A (S100A8; p=0.017) and calgranulin B (S100A9; p=0.022), were consistently up-regulated in high-grade dysplasia, as were protein levels for calgranulin A and B.


CONCLUSIONS
This is the first report of an association between the calprotectin complex, which is involved in chemotaxis of neutrophils, and the progression towards high-grade dysplasia in BE. It remains to be established whether differentially expressed proteins in biopsies form BE can be used to facilitate the diagnosis of advanced dysplasia in BE.
Bax
Dorine A
DA
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Siersema
Peter D
PD
Haringsma
Jelle
J
Kuipers
Ernst J
EJ
Vos
Arthur J M
AJ
Van Dekken
Herman
H
Van Vliet
Arnoud H M
AH
Kusters
Johannes G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology*; D001706:Biopsy; D040501:Calgranulin A / Q000235:genetics*; D040502:Calgranulin B / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged
D040501:Calgranulin A; D040502:Calgranulin B