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Daniel Vallböhmer, MD; Jeffrey H. Peters, MD; Hidekazu Kuramochi, MD; Daniel Oh, MD; Dong Yang, MD; Daisuke Shimizu, MD; Steven R. DeMeester, MD; Jeffrey A. Hagen, MD; Parakrama T. Chandrasoma, MD; Kathleen D. Danenberg, BSc; Peter V. Danenberg, PhD; Tom R. DeMeester, MD

Arch Surg. 2006;141:476-482.

Hypothesis  Cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) are useful biological determinants in targeted therapy for esophageal adenocarcinoma.

Design  Prospective analysis.

Setting  University tertiary referral center.

Patients  Sixteen patients with squamous mucosa and normal results of a pH study without mucosal injury (control group), 15 with Barrett esophagus (metaplasia group), and 44 with adenocarcinoma (carcinoma group).

Interventions  Biopsy specimens were obtained 3 cm above the gastroesophageal junction. Dysplastic tissue was additionally isolated from 9 of the patients in the carcinoma group. After laser-capture microdissection, quantitative real-time polymerase chain reaction was used to measure gene expression across the spectrum of the metaplasia-dysplasia-carcinoma sequence.

Main Outcome Measures  Expression of COX-2, VEGF, and EGFR in each patient group.

Results  Expression of both COX-2 and VEGF was significantly up-regulated in patients with metaplasia, dysplasia, and cancer compared with controls (P<.01). Expression levels of both were significantly higher in cancer than in the metaplasia group (P<.05) and increased sequentially from metaplasia to dysplasia to cancer. Expression of VEGF was significantly higher in the dysplastic tissue than in nondysplastic Barrett epithelium (P<.05). No change in expression levels of EGFR was seen in the histologic progression to esophageal adenocarcinoma.

Conclusion  Gene expression data suggest that pharmacologic inhibition of COX-2 and VEGF may be useful adjuncts in targeted therapy for esophageal adenocarcinoma.

Author Affiliations: Departments of Surgery (Drs Vallböhmer, Oh, S. R. DeMeester, Hagen, and T. R. DeMeester), Biochemistry and Molecular Biology (Drs Kuramochi, Shimizu, and Danenberg), Preventive Medicine (Dr Yang), and Pathology (Dr Chandrasoma), Keck School of Medicine, University of Southern California, Los Angeles; Department of Surgery, School of Medicine and Dentistry, University of Rochester, Rochester, NY (Dr Peters); Norris Comprehensive Cancer Center, Los Angeles (Drs Kuramochi, Yang, Shimizu, and Danenberg); and Response Genetics, Los Angeles (Ms Danenberg).