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Fatty Acid Synthase Expression in Barrett's Esophagus: Implications for Carcinogenesis

Ishimura, Norihisa MD*; Amano, Yuji MD; Sanchez-Siles, Alvaro Adolfo MD*; Fukuhara, Hiroyuki MD*; Takahashi, Yoshiko MD; Uno, Goichi MD*; Tamagawa, Yuji MD*; Mishima, Yuko MD*; Yuki, Takafumi MD; Ishihara, Shunji MD*; Kinoshita, Yoshikazu MD*

Journal of Clinical Gastroenterology:
doi: 10.1097/MCG.0b013e318207f240
ALIMENTARY TRACT: Original Articles
Abstract

Goals: To investigate the relationship between fatty acid synthase (FASN) expression and the clinicopathological characteristics of Barrett's esophagus and its carcinogenesis.

Background: FASN, a key enzyme of the fatty acid biosynthetic pathway, is overexpressed not only in various types of cancer, but also in premalignant conditions. Therefore, FASN overexpression is considered to be indicative of a possible premalignant stage.

Study: Patients (N=354) with endoscopically and histologically proven Barrett's esophagus were enrolled. Mucin phenotyping of Barrett's esophagus, expression of FASN and COX-2, cellular proliferation, and apoptosis were evaluated immunohistochemically in biopsy samples, and factors influencing FASN expression were determined by multivariate logistic regression analysis. To evaluate if gastric reflux induces FASN expression, esophageal adenocarcinoma cells were treated with bile acid and low pH, and the effect of a FASN inhibitor on cell proliferation was assessed.

Results: Expression of FASN protein was observed in 52.2% of patients with Barrett's esophagus by immunohistochemistry; this expression pattern was retained in esophageal adenocarcinoma. Intestinal mucin phenotype, COX-2, increased stromal angiogenesis, and elevated proliferating cell nuclear antigen index were confirmed to be positive independent factors for FASN expression. In the esophageal adenocarcinoma cell line SEG-1, FASN mRNA was induced by bile acid with low pH. Cell proliferation was strongly suppressed by the FASN inhibitor C75.

Conclusions: FASN is strongly expressed in the intestinal mucin phenotype of Barrett's esophagus, in which Barrett's glandular cells display elevated cellular proliferation, angiogenesis, and COX-2 expression. Exposure of the lower esophagus to bile acid with low pH may induce FASN in Barrett's esophagus.

Author Information

*Department of Gastroenterology and Hepatology, Shimane University, School of Medicine

Division of Gastrointestinal Endoscopy, Shimane University Hospital, Izumo, Japan

Declaration of Funding Sources: None.

Reprints: Yuji Amano, MD, Division of Gastrointestinal Endoscopy, Shimane University Hospital, 89-1, Enya-cho, Izumo-shi, Shimane 693-8501, Japan (e-mail: amano@med.shimane-u.ac.jp).

Received May 27, 2010

Accepted November 18, 2010

© 2011 Lippincott Williams & Wilkins, Inc.