Expression of alpha-methylacyl-coenzyme A racemase in dysplastic Barrett's epithelium

Although identification of epithelial dysplasia in Barrett's esophagus (BE) is critically important because of a significant risk of progression to invasive adenocarcinoma, the diagnosis of dysplasia may be challenging. Among confounding factors are interobserver variability, tangential sectioning, and severe mucosal inflammation leading to architectural and cytologic atypia similar to that of dysplasia. alpha-methylacyl-coenzyme A racemase (AMACR) is an enzyme involved in beta-oxidation of branched fatty acids and an established marker of prostate cancer. It is expressed in colon adenomas and adenocarcinomas but not in normal colonic epithelium suggesting a role in development of gastrointestinal malignancies. We investigated whether expression of AMACR can be used to identify dysplasia of BE and to distinguish it from reactive atypia. Ninety-six routinely processed biopsy and/or resection specimens (23 negative for dysplasia; 19, low-grade dysplasia; 22, high-grade dysplasia; 16, reactive atypia; and 16, esophageal adenocarcinoma) were immunostained using a monoclonal anti-AMACR antibody p504S. AMACR staining was uniformly negative in the groups negative for dysplasia and with reactive atypia. Only 2 (11%) of 19 specimens with low-grade dysplasia showed positive immunostaning, compared with 14 (64%) of 22 in high-grade dysplasia group. Of 16 specimens, 12 (75%) showed positive staining for AMACR in the adenocarcinoma group. Our data suggest that AMACR immunoreactivity is moderately sensitive in identification of high-grade dysplasia in BE and is highly specific in distinguishing high-grade dysplasia from reactive atypia. Further validation and prospective studies are warranted.