Immunohistochemical Characterization of Pancreatic Adenocarcinomas Arising in Association with Intraductal Papillary Mucinous Neoplasms.
Agnieszka K Witkiewicz, Jonathan Brody, Jessica Kline, Charles J Yeo, Peter McCue, N Volkan Adsay, Ralph H Hruban. Thomas Jefferson University, Philadelphia, PA; Johns Hopkins University, Baltimore, MD; Emory University, Atlanta, GA
Background: Most pancreatic adenocarcinomas (PAs) arise from pancreatic intraepithelial neoplasia (PanIN) for which molecular and immunohistochemical features have been well characterized. However, less studied are the PAs that arise from another precursor, intraductal papillary mucinous neoplasm (IPMN). In this study we correlated the pathology of 22 PA arising in association withan IPMN with immunohistochemical markers implicated in PA pathogenesis.
Design: The criteria for the inclusion in the study included radiologically and macroscopically visible cystic dilatation of pancreatic duct and presence of well defined papillae on histologic review. Histologic type of IPMN and invasive carcinoma was recorded for all cases. Immunohistochemical labeling for DPC4, p53, p16, Ki67, CDX2, MUC1, MUC2 was preformed on all cases.
Results: Nine IPMNs were intestinal, 6 pancreaticobilliary, 5 gastric and 2 mixed type. All cases showed at least focal high-grade dysplasia (carcinoma in situ). Associated PA was colloid in 4 cases, tubular in 16 and tubular with mucinous features in 2 cases. PAs arising from intestinal and gastric IPMNs tend to be better differentiated than those arising from pancreaticobilliary IPMN. MUC2 and CDX2 positivity were seen in the intestinal type IPMN, mucinous PA, and in the tubular carcinomas with mucinous features. DPC4 loss was seen in 4 of 9 tubular PA arising from pancreaticobilliary IPMN and only one arising from intestinal IPMN. Loss of p16 occurred in both tubular and mucinous PA. P53 expression was seen only in tubular PA.
Conclusions: PAs arising from IPMNs have a number of unique and similar molecular features to other precursors. Molecular classification of these lesions may provide valuable prognostic information and reveal potential early targets that may be shared with PanIN precursor lesions.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 213, Wednesday Morning