Differentiation markers in pancreatic head adenocarcinomas: MUC1 and MUC4 expression indicates poor prognosis in pancreatobiliary differentiated tumours

AIMS: To examine how accurately immunohistochemical markers discriminate between pancreatobiliary and intestinal-type adenocarcinomas in the pancreatic head and to explore the prognostic importance of these markers among each of these histological types. METHODS AND RESULTS: Histopathological features of 114 consecutively resected adenocarcinomas of pancreatobiliary (n = 67) and intestinal (n = 47) type of differentiation were recorded according to a standardized protocol. Immunohistochemistry for cytokeratin (CK) 7, CK20, MUC1, MUC2, MUC4 and CDX2 was performed on tissue microarrays. Classification of the adenocarcinomas based on immunohistochemistry was compared with the morphological evaluation of histological type. Presence of CK7 and MUC4, and absence of CDX2, were independent predictors of pancreatobiliary versus intestinal type. Using these markers to optimize immunohistochemical classification, agreement between immunohistochemical and morphological classification was only moderate (κ = 0.53). In pancreatobiliary differentiated tumours, MUC1 and/or MUC4 expression was an independent prognostic factor (hazard ratio 2.02, 95% confidence interval 1.02, 3.98) when adjusting for nodal involvement, vessel involvement and tumour size. In intestinally differentiated tumours, none of the markers was significantly associated with prognosis. CONCLUSIONS: Agreement between immunohistochemical and morphological classification of pancreatic head adenocarcinomas is moderate. In pancreatobiliary adenocarcinomas, MUC1 and/or MUC4 expression indicates a particularly poor prognosis.