Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis B Runjan Chetty MB ChB, FRCPath, FRCPC, DPhil a, * , Stefano Serra MD a , Sima Salahshor PhD b , Khaled Alsaad MD, FRCPC a , Warren Shih BSc a , Hagen Blaszyk MD c , James R. Woodgett PhD b , Ming-Sound Tsao MD, FRCPC a a Department of Pathology, University Health Network/Toronto Medical Laboratories, University of Toronto, Toronto, Ontario, Canada M5G 2M9 b Department of Medical Biophysics, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9 c Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA Received 15 September 2005; revised 31 October 2005; accepted 2 November 2005 Summary Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer where up to 90% of cases are thought to have impaired Wnt signaling. It is less frequently involved in conventional ductal pancreatic adenocarcinoma. This pathway has not been explored in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously and formed the basis of this study. A tissue microarray of 18 cases of IPMN was stained for proteins involved in the Wnt pathway: adenomatous polyposis coli (APC), pan–b-catenin, axin 2, glycogen synthase 3ab and 3b, c-myc, E-cadherin, and cyclin D1. The IPMNs were classified as 8 adenomas, 3 borderline, and 7 cases with carcinoma in situ and/or invasive carcinoma, occurring in 13 females, and the overall age range was 45 to 73 years. Immunohistochemical analysis showed nuclear b-catenin staining in 7 (39%) of the 18 cases. The cases with nuclear b-catenin localization included 1 adenoma, 2 borderline IPMN, and 4 carcinomas in situ and/or invasive carcinomas. Seven cases showed absence of APC immunostaining and these included 4 cases with nuclear b-catenin localization. Fourteen cases displayed marked diffuse up-regulation of c-myc protein, and 12 cases also showed diffuse cyclin D1 protein overexpression. E-cadherin expression was intense and membrane in location (comparable to normal tissue) in 6 of 8 adenomas (no tissue was available in 1 case). Decreased E-cadherin staining was noted in 8 cases where tissue was available for assessment. There was progressive decrease in membrane staining of E-cadherin in 2 of 3 borderline lesions, 1 of 2 carcinomas in situ, and 4 of 5 invasive carcinomas. All other immunostains were either normal in distribution or did not show any correlation with b-catenin or clinicopathologic parameters. In conclusion, 7 (39%) of 18 cases of IPMN in this study demonstrated abnormal localization of b-catenin, 4 of which also lacked APC expression. 0046-8177/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2005.11.002 B This study was supported by Canadian Institutes of Health Research grant MOP-49585. 4 Corresponding author. Department of Pathology, Princess Margaret Hospital, Toronto, Ontario, Canada M5G 2M9. E-mail address: runjan.chetty@uhn.on.ca (R. Chetty). Keywords: Pancreas; Intraductal papillary mucinous neoplasm; Wnt signaling; b-catenin; APC; E-cadherin Human Pathology (2006) 37, 212–217 www.elsevier.com/locate/humpath