The relationship between loss expression of DPC4/Smad4 gene and carcinogenesis of pancreatobiliary carcinoma.
OBJECTIVE
To clarify the relationship between loss of DPC4 gene expression and pathogenesis of pancreatobiliary carcinoma.


METHODS
75 slides of normal duct (20), hyperplasia (15), dysplasia (15), invasive carcinoma (25) from patients with pancreatic diseases including pancreatic carcinoma (25 patients), chronic pancreatitis (6), pancreas injury (2) and 71 slides of common bile duct (CBD) carcinoma (38), gallbladder carcinoma (18), hilar bile duct (HBD) carcinoma (15) from patients with primary biliary tract carcinoma were analyzed for the expression of DPC4 protein by immunohistochemical staining.


RESULTS
All specimens from 20 cases of normal duct and 15 cases of hyperplasia showed marked expression of DPC4 protein. The frequency of loss expression of the DPC4 gene was 33% in dysplasia, and 48% in invasive carcinoma. There was a significant statistical difference between hyperplasia and dysplasia (P<0.01) and in dysplasia vs invasive carcinoma (P<0.05). The frequency of loss expression of the DPC4 gene was 47.3% in CBD carcinoma, 11% in gallbladder carcinoma, and 13% in HBD carcinoma. The frequency of loss expression of the DPC4 gene was significantly different in CBD carcinoma vs gallbladder carcinoma and HBD carcinoma (P<0.01).


CONCLUSIONS
Inactivation of the DPC4 gene occurs late in the neoplastic progression of pancreatic carcinoma. The frequency of DPC4 gene alternation was different in various locations of biliary tract carcinoma. In CBD carcinoma, this frequency is similar to that in pancreatic carcinoma, indicating their similar molecular alternations.
Tang
Zhao-Hui
ZH
Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. tangzh45@sina.com
Zou
Sheng-Quan
SQ
Hao
You-Hua
YH
Wang
Bao-Ju
BJ
Yang
Xiang-Ping
XP
Chen
Qi-Qi
QQ
Qiu
Fa-Zu
FZ
D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051901:Smad4 Protein; D013194:Staining and Labeling; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators