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Epithelial-Cadherin and ß-Catenin Expression Changes in Pancreatic Intraepithelial Neoplasia

¹ Department of Pathology, University Health Network-Ontario Cancer Institute/Princess Margaret Hospital and² Mount Sinai Hospital, Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

ABSTRACT

Purpose: Cadherins and associated catenins are important mediators of epithelial cell-cell adhesion, as well as the Wnt-signaling pathway. Significant changes in their expression or structure have been implicated in malignancy. This study aimed to investigate the epithelial-cadherin (E-cadherin) and ß-catenin expression changes during multistage, pancreatic ductal carcinogenesis.

Experimental Design: Ninety-four Whipple resection specimens were retrieved from the surgical pathology files of the University Health Network (Toronto, Canada), from which tissue microarray blocks containing 36 pancreatic ductal adenocarcinomas, 34 PanIN-1A lesions, 28 PanIN-1B lesions, 27 PanIN-2 lesions, 16 PanIN-3 lesions, and 32 normal ducts were constructed. The E-cadherin, ß-catenin, and the phosphorylated glycogen synthase kinase-3ß of the Wnt/ß-catenin pathway were immunohistochemically evaluated in these duct/PanIN lesions.

Results: There was marked increase in the cytoplasmic E-cadherin expression in PanIN lesions (P < 0.0001) and adenocarcinoma (P = 0.005) compared with normal pancreatic ducts. In contrast, reduced/loss of E-cadherin membranous expression was also significant in ductal adenocarcinoma compared with both the PanIN lesions (P < 0.0001) and normal ducts (P = 0.05). The ß-catenin expression showed significantly more frequent aberrant nuclear localization in high-grade PanIN lesions, particularly PanIN2 and in adenocarcinoma compared with normal ducts or low grade PanIN lesions (P < 0.0001). However, there was a lack of correlation between phospho^Ser9-glycogen synthase kinase-3ß cytoplasmic expression and ß-catenin aberrant nuclear expression (P = 0.07).

Conclusions: Aberration in the expression of E-cadherin and its associated ß-catenin is evident in pre-invasive (PanIN) neoplastic pancreatic duct cells, suggesting involvement of pathways leading to ß-catenin stabilization during pancreatic duct cell carcinogenesis.

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