Expression of the caudal-type homeodomain transcription factors CDX 1/2 and outcome in carcinomas of the ampulla of Vater

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.