The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

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H epatic resection and liver transplantation are aggressive, extirpative approaches to the treatment of selected patients for hepatocellular carcinoma (HCC) and are the only known potentially curative treatment options for this disease. Resection and transplantation are largely complimentary, not competing, treatments-resection for patients with preserved liver function and transplantation for patients with compromised liver function. Within each group, selection of patients for surgical therapy is currently based on morphologic criteria such as size, number of tumors, and degree of underlying liver disease.After resection, long-term survival can be expected in patients with solitary tumors regardless of size, especially when underlying fibrosis is minimal. 1 In fact, size has no significant impact on survival when microscopic vascular invasion is absent, as survival after resection of T1 tumors larger than 10 cm in diameter is similar to survival following resection of T1 tumors less than 5 cm. 1 Similarly, long-term survival can be expected when multiple tumors without vascular invasion are completely resected. 1 The establishment of strict morphologic criteria has significantly impacted the outcome after liver transplantation for HCC. Before the adoption of these criteria for transplantation, results with liver transplantation were poor. Recurrence rates ranged from 60% to 70%, 2,3 and the 5-year survival rate was less than 30%. 4,5 Since the implementation of more stringent selection criteria, survival rates after liver transplantation have been similar to those after resection for Abbreviations: HCC, hepatocellular carcinoma; AFP, alpha-fetoprotein; HR, hazard ratio; FNA, fine-needle aspiration.

Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small-sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear. Therefore, the first step to minimize the debate on these indications is to review the standard results from each treatment based on an extensive survey. The participants in this study were patients with HCCs less than 5 cm in diameter who were enrolled in The Liver Cancer Study Group of Japan. The survival rates in the HX (n = 8,010), PEI (n = 4,037), and TCAE (n = 841) groups were calculated in relation to the number of tumors and the clinical stage. In the clinical stage I cases with a solitary tumor less than 2 cm in diameter and in all clinical stages with a solitary tumor greater than 2 cm and in the clinical stage II cases with 2 tumors greater than 2 cm, the HX group showed higher survival rates than the nonsurgical groups. The HX group had a higher male/female ratio and a younger mean age than the PEI or TCAE group. The ratio of HBs antigen-positive cases/hepatitis C virus antibody-positive cases in the PEI group was lower than that in the corresponding HX group. In contrast, the PIVKA-II values in the HX group tended to be higher than in the PEI group. In conclusion, these findings will provide useful information for selection of a therapeutic modality for small-sized HCCs.

BACKGROUND Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base. METHODS In this study, the authors analyzed 12,118 patients with HCC in a Japanese nationwide data base who underwent liver resection between 1990 and 1999 and compared them with a previous analysis of patients between 1982 and 1989. All patients were evaluated for prognostic factors. RESULTS During the last decade, the increases in patients who were without hepatitis B virus surface antigen, who had small tumors, and who had portal vein invasion were noted. The 5‐year overall survival rates for patients with HCC improved to 50.5%, compared with < 40% in the previous analysis. A multivariate analysis using a stratified Cox proportional hazards model according to associated liver disease indicated that age, degree of liver damage, α‐fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were independent prognostic predictors for patients with HCC. Operative mortality decreased from 2.3% in 1990–1991 to 0.6% in 1998–1999. CONCLUSIONS Outcomes and operative mortality rates in patients with HCC improved during the last decade. Age, degree of liver damage, α‐fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were prognostic factors for patients with HCC who underwent liver resection. Cancer 2004. © 2004 American Cancer Society.