DPC4 (MADH4, SMAD4) is a nuclear
transcription factor shown to be genetically inactivated in over half of infiltrating ductal
adenocarcinomas of the pancreas. Immunohistochemical labeling for the DPC4 gene product using a
monoclonal antibody has recently been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic
adenocarcinomas. Mucinous
cystic neoplasms (MCNs) are a biologically less aggressive subtype of
pancreatic neoplasm that may show benign, borderline, or overtly malignant features. However, the role of DPC4 inactivation in the development of MCNs has not been examined. The immunohistochemical expression of Dpc4
protein was therefore examined in 36 mucinous
cystic neoplasms using this previously characterized
monoclonal antibody. The 36 mucinous
cystic neoplasms studied included 23
adenomas, 1
tumor with borderline potential, 5
tumors with
carcinoma in situ, and 7 invasive
carcinomas. Twenty-nine (100%) of the 29 noninvasive mucinous
cystic neoplasms strongly expressed Dpc4 in the neoplastic epithelium. In striking contrast, only one (14%) of seven infiltrating
carcinomas expressed Dpc4 in the neoplastic epithelium (p = 0.0001). The adjacent stroma retained expression of this
protein in all 36 cases. In invasive MCNs with loss of Dpc4 expression, areas of
carcinoma in situ were identified in the same
paraffin sections, and these areas of
carcinoma in situ retained expression of Dpc4. The frequent loss of Dpc4 expression in invasive MCNs indicates that genetic inactivation of Dpc4 occurs late in the neoplastic progression of these
tumors and suggests a relationship to the development of invasion.