Molecular determinants in targeted therapy for esophageal adenocarcinoma

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.