The Pattern of CDX2 Expression in Ampullary Adenocarcinomas Predicts Biliary Versus Intestinal Phenotype: Prognostic Implications
Lizette Vila Duckworth, Ahmad Alkhasawneh, Neelam Desai, Alex Sommerfeld, Xiaomin Lu, Thomas George, Tania Zuluaga Toro. University of Florida, Gainesville, FL
Background: CDX2 (caudal-related homeobox 2) is a nuclear transcription factor implicated in intestinal differentiation, and thus tumors with intestinal phenotype demonstrate CDX2 nuclear expression by immunohistochemistry (IHC) regardless of the organ of origin. We assessed the pattern of CDX2 expression in ampullary adenocarcinoma and its relation to different histologic subtypes and clinical parameters.
Design: Sixty-three cases of ampullary adenocarcinomas resected between 2000 and 2011 were assessed for CDX2 expression by IHC. Morphologic type (intestinal, biliary, or indeterminate), tumor stage, and measures of clinical outcome (death, recurrence) were recorded. Nuclear CDX2 expression was assessed as follows: negative (complete absence), heterogeneous (weak to moderate nuclear staining in <75% of tumor cells; pattern similar to background pancreas) and homogeneous (strong, diffuse nuclear staining in ≥75% of tumor cells; pattern similar to background duodenal epithelium) (adapted from Chu et al. 2005). For assessment of clinical outcome, only cases with homogeneous CDX2 expression were considered positive, while the negative and heterogeneous CDX2 cases were merged into one group.
Results: Seventeen cases were positive for CDX2 in a diffuse, homogeneous pattern, and 46 were CDX2 heterogeneous to absent. 88% of the CDX2 homogeneous cases were of intestinal subtype, while 93% of the heterogeneous to negative cases were either biliary or indeterminate subtype. Lymph node metastasis was significantly higher in the group with heterogeneous to absent CDX2 expression compared with cases with homogeneous CDX2 (p = 0.01).
|Homogeneous (n=17)||Heterogeneous/negative (n=46)|
|stage T1/T2||41% (7)||22% (10)|
|stage T3/T4||58% (10)||78% (36)|
|Lymph node involvement||12% (2)||37% (17)|
|Recurrence||6% (1)||28% (13)|
|Deceased||35% (6)||59% (27)|