Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile duct.
OBJECTIVE
Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC).


METHODS
The immunohistochemical method and RT-PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone-containing IHD, and ICC. All the specimens were from hepatic resection.


RESULTS
The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone-containing IHD and ICC, respectively. Among the specimens of stone-containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT-PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone-containing IHD and ICC, respectively.


CONCLUSIONS
Loss expression of DPC4/Smad4 gene was found both in stone-containing IHD and ICC. Dysplastic epithelium of stone-containing IHD had higher potential for malignant transformation.
Lee
King-Teh
KT
Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. ktlee@kmu.edu.tw
Chang
Wen-Tsan
WT
Wang
Shen-Nien
SN
Chuang
Shih-Chang
SC
Chai
Chee-Yin
CY
Hu
Shih-Wen
SW
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry*; D002137:Calculi / Q000209:etiology*; D018281:Cholangiocarcinoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D042882:Gallstones / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein / Q000096:biosynthesis* / Q000235:genetics*
D012333:RNA, Messenger; C497796:SMAD4 protein, human; D051901:Smad4 Protein