Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas - Comparison with conventional ductal adenocarcinomas

DPC4 (MADH4, SMAD4) encodes a nuclear transcription factor shown to be gene tically inactivated in over one-half of conventional infiltrating ductal ad enocarcinomas of the pancreas, Intraductal papillary mucinous neoplasms (IP MNs) of the pancreas have been suggested to be distinct neoplasms with a si gnificantly less aggressive course than conventional ductal adenocarcinomas of the pancreas, but molecular comparisons of these tumor types have previ ously been impaired by technical difficulties. Recently, immunohistochemica l labeling for the DPC4 gene product has been shown to be an extremely sens itive and specific marker for DPC4 gene alterations in pancreatic adenocarc inomas. Therefore, we analyzed the immunohistochemical expression of Dpc4 p rotein in 79 IPMNs using a previously characterized monoclonal antibody. Tw enty-nine of the IPMNs also had an associated infiltrating adenocarcinoma a vailable for analysis. The labeling patterns observed were compared to thos e we have previously reported for conventional ductal carcinomas. All 79 of the intraductal components of the IPMNs strongly expressed Dpc4 protein. I n 77 of the 79 cases (97%), the labeling was diffusely positive, and in 2 o f the 79 (3%) the labeling was focally positive. Dpc4 expression was seen i n 28 (97%) of the associated 29 invasive cancers. The one infiltrating carc inoma that showed loss of Dpc4 expression was associated with an Intraducta l component which showed focal loss of Dpc4 expression. The strong and almo st universal expression of Dpc4 in IPMNs contrasts sharply with the loss of Dpc4 expression seen in approximately 30% of in situ adenocarcinomas of th e pancreas (so-called pancreatic intraepithelial neoplasms, grade 3; P < 0. 001) and in 55% of pancreatic duct carcinomas (P < 0.0001). Differences in Dpc4 expression between IPMNs and ductal carcinomas suggest a fundamental g enetic difference in tumorigenesis, which may relate to the significantly b etter clinical outcomes observed for IPMNs.