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


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.


CONCLUSIONS
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.
Toga
Tomoko
T
Department of Cardiovascular and Digestive Surgery, Shimane University School of Medicine, Izumo 693-8501, Japan.
Nio
Yoshinori
Y
Hashimoto
Koji
K
Higami
Tetsuya
T
Maruyama
Riruke
R
D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators