Prognostic Value of Digitally Quantified CDX2 Expression in Pancreatic Ductal Adenocarcinoma Without Intestinal Differentiation

BackgroundCDX2 is a transcription factor critical for intestinal development and differentiation. While its prognostic value is established in colorectal cancer, its significance in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Given the overlap of intestinal-type features in intraductal papillary mucinous neoplasms (IPMNs), clarifying the role of CDX2 in PDAC and IPMN may provide insights into tumor biology and prognostic markers.MethodsWe retrospectively analyzed 35 PDAC and 42 IPMN-associated carcinoma (IPMC) resected lesions. Immunohistochemistry for CDX2 and intestinal differentiation markers (ATOH1, MUC2, GPA33) was performed. CDX2 expression was semi-quantified using an H-score derived from whole-slide image analysis with QuPath. Associations between CDX2 expression and disease-free survival (DFS) were assessed using Kaplan-Meier and Cox regression analyses.ResultsCDX2 expression was observed in 43% of PDAC and 50% of IPMC. In IPMC, CDX2 positivity was often accompanied by downstream markers, suggesting preserved intestinal-type differentiation. In contrast, CDX2-positive PDAC rarely expressed GPA33 or MUC2, indicating divergence from the intestinal cascade. Higher CDX2 H-scores were significantly associated with lower recurrence (p = .027). ROC analysis showed fair predictive ability with an AUC of 0.74 (p = .008). Although multivariate analysis was not significant, subgroup analysis showed that in PDAC with lymph node metastasis, high CDX2 expression was associated with longer DFS (p = .014).ConclusionsDigitally quantified CDX2 expression may serve as a favorable prognostic biomarker in PDAC, distinct from its role in maintaining intestinal-type differentiation in IPMN. Validation in larger, multicenter cohorts is warranted.