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Expression of the Caudal-Type Homeodomain Transcription Factors CDX 1/2 and Outcome in Carcinomas of the Ampulla of Vater

From the Departments of Pathology, Surgery, Oncology, and Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD

Address reprint requests to Andrew V. Biankin, MBBS, PhD, Department of Surgery, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 771, Baltimore, MD 21205; e-mail: abianki1{at}jhmi.edu

PURPOSE: Adenocarcinomas of the ampulla of Vater demonstrate a characteristic histology but vary significantly in outcome. As a consequence, prognostic factors for these cancers are poorly defined. The caudal-type homeodomain transcription factors 1 (CDX1) and 2 (CDX2) regulate axial development and intestinal differentiation. We assessed the expression of these putative intestinal epithelial-specific transcription factors and their influence on patient outcome.

PATIENTS AND METHODS: Fifty-three resected carcinomas of the ampulla of Vater, 31 pancreatic ductal adenocarcinomas, and 15 extrahepatic biliary carcinomas were analyzed for CDX1 and CDX2 expression using immunohistochemistry.

RESULTS: Forty percent of carcinomas of the ampulla of Vater but less than 5% of pancreatic and biliary adenocarcinomas expressed CDX. Expression of CDX was associated with a better prognosis (P = .0009). Individually, both CDX1 (P = .02) and CDX2 (P = .02) expression were associated with a survival advantage on univariate analysis. Advanced T stage (P = .02), lymph node metastases (P = .004), and vascular space invasion (P = .0009) were associated with a poor prognosis. Multivariate analysis revealed vascular space invasion (P = .01) and CDX expression (P = .01) to be independent prognostic factors.

CONCLUSION: Expression of CDX was an independent marker of outcome in patients with resected adenocarcinoma of the ampulla of Vater. Expression of CDX may distinguish good prognosis intestinal-like tumors, which potentially arise within intestinal epithelium, from poorer prognosis pancreatobiliary tumors, which arise in adjacent pancreatic and/or biliary ductal epithelium.

Supported by National Institutes of Health grant Nos. DK-56211 (S.D.L.) and T32-DK 077130 (Johns Hopkins Training Grant in Gastrointestinal Surgical Research), the family of Margaret Lee, the Ken Warren Fellowship of the International Hepato-Pancreato-Biliary Association (A.V.B.), the Neil Hamilton Fairley postdoctoral fellowship from the National Health and Medical Research Council of Australia (A.V.B.), and the Paul K. Neumann Professorship in Pancreatic Cancer at Johns Hopkins University (S.D.L.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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