Fatty Acid Synthase Expression in Barrett's Esophagus and Its Detection in Endoscopic Surveillance

Abstract

Background and Aims: Fatty acid synthase (FAS) is a key enzyme of fatty acid synthesis from carbohydrate. FAS also expresses in regenerating epithelium, intestinal metaplastic epithelium, and dysplastic lesions of the stomach, suggesting that FAS expression may be indicative of a pre-cancerous stage. We found FAS expression in all the cases with Barrett's cancer and in some cases with Barrett's esophagus (BE) by immunohistochemical and RT-PCR methods. Therefore, FAS expression may play an important role in BE and its carcinogenesis. In this study, the significance of FAS expression in BE and the endoscopic method for detecting FAS-positive BE were investigated. Patients and Methods: 180 patients (mean age 65.0+/−12.3 years, M:F = 124:56) histologically proven BE were enrolled. Prior to endoscopic examination, they were assessed for GERD and administration of PPIs and NSAIDs using a structured questionnaire. H. pylori infection and endoscopic findings of reflux esophagitis, hiatal hernia, and gastric mucosal atrophy were also investigated. Using immunohistochemistry, mucin-phenotyping of BE; expression of FAS, COX-2, and Cdx2; cellular proliferation and apoptotic activity were evaluated in biopsy samples. Factors influencing FAS expression were determined by logistic multivariate analysis. Fifty consecutive patients with BE were surveyed by crystal violet chromoendoscopy and the relationship between the pit pattern and FAS expression was also evaluated by RT-PCR methods and immunohistochemistry. The pit pattern was classified as previously proposed by us (Dig Liv Dis 2006). Results: FAS expression was observed in 52.6% of patients with BE. BE with FAS expression showed an expression of COX-2 protein, an accelerated cellular proliferation and in inhibited apoptosis. Presence of reflux esophagitis (OR 4.28, p = 0.045), intestinal mucin-phenotype (OR 6.78, p = 0.008), Cdx2 protein (OR 13.29, p = 0.038), COX-2 protein (OR 1.76, p = 0.021), elevated PCNA index (OR 1.09, p = 0.009), and lower apoptosis index (OR 0.75, p = 0.039) were confirmed to be positive independent factors for the expression of FAS. FAS-positive BE significantly showed an open-type pit pattern (p < 0.001). Discussion and Conclusion: FAS is strongly expressed in intestinal mucin-phenotype BE with accelerated cell proliferation and inhibited apoptosis, suggesting that FAS expression is a marker for malignant potential of BE. Moreover, BE with FAS expression could be easily detected by crystal violet chromoendoscopy and this may play an important role in endoscopic Barrett's surveillance. However, the role of FAS for the carcinogenesis of BE should be more clearly elucidated in the future study.