Molecular determinants in targeted therapy for esophageal adenocarcinoma

Daniel Vallböhmer, Jeffrey H. Peters, Hidekazu Kuramochi, Daniel Oh, Dong Yang, Daisuke Shimizu, Steven R. DeMeester, Jeffrey A. Hagen, Parakrama T. Chandrasoma, Kathleen D. Danenberg, Peter V. Danenberg, Tom R. DeMeester, John T. Vetto, Fiemu Nwariaku, Fabrizio Michelassi

    Research output: Contribution to journalArticle

    24 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)476-482
    Number of pages7
    JournalArchives of Surgery
    Volume141
    Issue number5
    DOIs
    StatePublished - May 1 2006

    ASJC Scopus subject areas

    • Surgery

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    Vallböhmer, D., Peters, J. H., Kuramochi, H., Oh, D., Yang, D., Shimizu, D., DeMeester, S. R., Hagen, J. A., Chandrasoma, P. T., Danenberg, K. D., Danenberg, P. V., DeMeester, T. R., Vetto, J. T., Nwariaku, F., & Michelassi, F. (2006). Molecular determinants in targeted therapy for esophageal adenocarcinoma. Archives of Surgery, 141(5), 476-482. https://doi.org/10.1001/archsurg.141.5.476