OBJECTIVES: 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.
OBJECTIVES: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.
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Authors: Tamotsu Kuroki; Francesco Trapasso; Takeshi Shiraishi; Hansjuerg Alder; Koshi Mimori; Masaki Mori; Carlo M Croce Journal: Cancer Res Date: 2002-04-15 Impact factor: 12.701