The dissociated expression of protein and messenger RNA of DPC4 in human invasive ductal carcinoma of the pancreas and their implication for patient outcome

Anticancer Res. 2004 Mar-Apr;24(2C):1173-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / surgery
  • Chemotherapy, Adjuvant
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Smad4 Protein
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Treatment Outcome

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators