Mutations of beta-catenin and AXIN I genes are a late event in human hepatocellular carcinogenesis.
BACKGROUND
Hepatocellular carcinoma (HCC) is a well-known cancer involving the Wnt pathway in its carcinogenesis.


OBJECTIVE
However, it is not clear whether these genetic changes are early genetic events in hepatocarcinogenesis or not.


METHODS
In this study, we performed mutational analysis of the beta-catenin and AXIN I genes, and immunohistochemistry for beta-catenin in a series of 114 hepatocellular nodular lesions, including premalignant lesions such as low-grade dysplastic nodules (LGDNs) and high-grade dysplastic nodules (HGDNs).


RESULTS
In the present study, mutations of the beta-catenin and AXIN I genes were detected in 16% (13 out of 81) and 6.2% (five of 81) of the HCCs, respectively. However, no mutations were found in 14 LGDNs and 19 HGDNs. Moreover, abnormal nuclear beta-catenin immunostaining was observed in 30 of 81 HCCs, but not in dysplastic nodules.


CONCLUSIONS
Taken together, our data suggest that beta-catenin stabilization because of either beta-catenin or AXIN I mutation might be a late event for malignant progression rather than an early genetic event involving the initiation of HCC development.
Park
Jik Young
JY
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Park
Won Sang
WS
Nam
Suk Woo
SW
Kim
Su Young
SY
Lee
Sug Hyung
SH
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Park
Cheol Keun
CK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin
D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin