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

Abstract

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 (j = 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.

Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

“…Profiling of ductal differentiation markers, such as mucins and cytokeratins, may aid in tumor characterization and monitoring passage-derived deviations. Regarding to mucins, MUC1 and MUC4 seem to play a key role in the progression of the disease and have been proposed as markers of poor prognosis whereas MUC2 plays usually a tumor suppressor role and is rarely detectable in aggressive pancreatic tumors [20][21][22][23] .In our study, MUC1 and MUC4 were present in 100% and 80% tumors, respectively, whereas only 20% of primary tumors were positive for MUC2. With respect to cytokeratins, although the expression of a single CK is of little diagnostic value, the expression pattern of CK7/CK20 in epithelial tumors has been proposed as useful in distinguishing primary from metastatic carcinomas of varied origins [24,25].…”

Better Outcome of XELOX Chemotherapy in Patients with Advanced Intestinal-Type Adenocarcinoma of the Ampulla of Vater

“…Pancreatobiliary-type adenocarcinoma has a phenotype similar to that of pancreatic ductal adenocarcinoma. The tumor glands consist of cuboidal or columnar cells, usually without nuclear stratification, associated with more abundant desmoplastic stroma (Kimura et al 1994;Fischer and Zhou 2004) and express cytokeratin 7 (CK7), mucin 1 (MUC1) and mucin 5AC (MUC5AC) (Chu et al 2005;Westgaard et al 2009). …”

Elaidic Acid, a <b><i>Trans</i></b>-Fatty Acid, Enhances the Metastasis of Colorectal Cancer Cells

“…The expressions of stem cell markers (NS, CD133, and Oct4), intestinal differentiation markers (MUC1, MUC2, and CDX2) [19] , and undifferentiation marker (c-Myc) were examined in OA-and EA-treated cells ( Fig. 2 c, d).…”