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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recently, abnormal activation of the Wnt pathway has been found to be involved in the carcinogenesis of HCC. However, the relationship between genetic changes in the Wnt pathway-associated genes and its protein expression has not been studied in patients with HCC and cirrhotic nodules. The purpose of this study is to explore the contribution of inappropriate activation of the Wnt pathway in liver carcinogenesis.Somatic mutation in exons 3-5 of AXIN1 and exon 3 of beta-catenin were analyzed by direct sequencing and expression of axin and beta-catenin proteins by immunohistochemistry in a series of 36 patients with HCC and cirrhosis.The AXIN1 and beta-catenin gene mutations were observed in 25% (9/36) and 2.8% (1/36) of HCCs, respectively. All mutations detected in AXIN1 and beta-catenin genes were missense point mutations. Abnormal nuclear expression of beta-catenin was observed in 11 of 36 cases of HCCs (30.6%), but not in cirrhotic nodules. Reduced or absent expression of axin was seen in 24 of 36 HCCs (66.7%). The abnormal expression of beta-catenin and axin proteins was closely correlated with mutations of AXIN1 and beta-catenin (P0.0001 and P = 0.008, respectively).These data suggest that mutation of AXIN1 gene is a frequent and late event for HCC associated with cirrhosis, and is correlated significantly with abnormal expression of axin and beta-catenin. Therefore, activation of Wnt signaling through AXIN1 rather than beta-catenin mutation might play an important role in liver carcinogenesis.

We retrospectively reviewed the hospital records of patients with early gastric carcinoma to compare the clinicopathologic findings in young (age40 years, n = 72) and older (age70 years, n = 51) patients during the period 1991-2000. Overall survival was the main outcome measure. There was a significant difference in depth of invasion; carcinoma invaded the mucosal layer in 65.3% of the young patients and in 39.2% of the older patients (P0.05). The 5-year survival rates of young and older patients did not differ statistically (97.2% versus 94.5%; P = 0.254). The prognosis of young patients with early gastric carcinoma was similar to that of older patients with early gastric carcinoma, and the belief that the prognosis of gastric carcinoma in young patients is poorer than in aged patients should be abandoned. Early detection is most important to achieve the good prognosis.