Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma.
OBJECTIVE
DPC4 is a tumor suppressor gene on chromosome 18q21.1 that has high mutant frequencies in pancreatic carcinogenesis. The purpose of this study was to investigate the role of DPC4 alterations in tumorigenesis and progression of pancreatic carcinomas.


METHODS
We studied the immunohistochemical markers of DPC4 in 34 adenocarcinomas and 16 nonmalignant specimens from the pancreas. The 16 nonmalignant specimens from the pancreas included 8 non-neoplastic cysts and 8 normal pancreatic tissues. The relationship between DPC4 alterations and various clinicopathological parameters was evaluated by chi-square test or Fisher's exact test. Survivals were calculated using Kaplan-Meier method (by a log-rank test).


RESULTS
All the 16 nonmalignant cases of the pancreas showed expression of DPC4 gene. Loss of DPC4 expression was seen in 8 of 34(23.5%) pancreatic adenocarcinomas. The frequency of loss of DPC4 expression was higher in poorly differentiated adenocarcinoma (G3) than in well and moderately differentiated adenocarcinoma (G1 and G2) histologically (P=0.037). Loss of DPC4 expression of the patients at TNM stage IV was also higher than that of the patients at TNM stages I, II and III (60.0% at stage IV, versus 14.3% at stage I, 18.2% at stage II, and 18.2% at stage III) (P=0.223). The mean and median survival in patients with DPC4 expression was longer than those in patients with loss of DPC4 expression. Kaplan-Meier survival analysis demonstrated patients with DPC4 expression had a higher survival rate than patients with loss of DPC4 expression, but the difference did not reach statistical significance (P=0.879).


CONCLUSIONS
This study suggests that DPC4 is involved in the development of pancreatic carcinoma and is a late event in pancreatic carcinogenesis, DPC4 expression may be a molecular prognostic marker for pancreatic carcinoma.
Hua
Zhan
Z
Peking Union Medical College, China-Japan Friendship Institute of Clinical Medical Sciences, Beijing 100029, China. huazhan@hotmail.com
Zhang
Yuan-Chun
YC
Hu
Xiao-Ming
XM
Jia
Zhen-Geng
ZG
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D012016:Reference Values; D051901:Smad4 Protein; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators