Loss of WWOX expression in human extrahepatic cholangiocarcinoma.
OBJECTIVE
WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1. To investigate the role of the WWOX gene in the development of extrahepatic cholangiocarcinoma (ECC), 30 tissue samples of ECC were examined.


METHODS
Loss of heterozygosity (LOH), real time reverse transcription PCR (RT-PCR), and immunohistochemistry were used to assess the role of WWOX in cholangiocarcinoma.


RESULTS
LOH was observed in 50% of cases, loss of mRNA was observed in 46.67% of the cases and loss of WWOX protein expression was found in 56.67% of ECC tissue samples. LOH, mRNA, and protein expression had a significant correlation with histological grading. The correlation coefficients were -0.623, -0.475 and -0.543, respectively. However, WWOX expression had no correlations with other clinicopathological factors such as age, gender, clinical staging or the status of preoperative hepatic function (p > 0.05). Poorly differentiated ECC had significantly lower expression of WWOX than that of moderately or well differentiated ones (p < 0.05).


CONCLUSIONS
Loss of WWOX may be involved in the tumorigenesis of extrahepati cholangiocarcinoma.
Wang
Mei
M
Department of Oncology, Changhai Hospital, 200433, Shanghai, China.
Gu
Jun
J
Wang
Yajie
Y
Gong
Biao
B
D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000074584:WW Domain-Containing Oxidoreductase
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human