The Dissociated Expression of Protein and Messenger RNA of DPC4 in Human Invasive Ductal Carcinoma of the Pancreas and their Implication for Patient Outcome

Abstract

Background: The loss of expression of Dpc4 protein (pDpc4) has been demonstrated in about half of invasive ductal carcinoma (IDC) of the pancreas, but the expression of DPC4-mRNA remains to be evaluated. The present study assessed the comparative expression of pDpc4 and DPC4-mRNA in pancreatic IDC and their implication for patient outcome. Materials and Methods: In the freshly separated specimens of 21 IDCs and the paraffin-embedded specimens of 88 resectable IDCs, the expression of mRNA was assessed by in situ hybridization and the expression of pDpc4 was assessed by immunohistochemistry. Results: In the freshly separated specimens, DPC4-mRNA was expressed in 71% of the IDC, but pDpc4 expression was lost in 76% of the IDC. In 88 resectable IDCs, pDpc4 expression was lost in 75 (85.2%) and loss of pDpc4 expression was significantly correlated with the grade of nodal involvement (p=0.0265). Furthermore, the survival rate of the pDpc4 (-) group was significantly lower than that of the pDpc4 (+) group (p=0.0391). Adjuvant chemotherapy (ACT) significantly improved the survival rate and, in the ACT group, pDpc4 (-) patients had a significantly lower survival rate than the pDpc4 (+) patients. Conclusion: In human pancreatic IDC, although DPC4-mRNA was usually expressed, the expression of pDpc4 was lost. The expression of pDpc-4 is an indicator of better prognosis and response to ACT.