The 3 cm cutoff seems to best determine the biological behavior and clinical prognosis of patients undergoing partial hepatectomy for early stage HCC. Overall, HCC smaller than 3 cm in diameter was closely related with a better prognosis which reflected the relatively benign pathobiological features at an early developmental stage. As HCC > 3 cm exhibited a tendency towards more aggressive behavior, we suggest that HCC ≤ 3 cm in diameter should be used as a critical size of SHCC at which curative treatment achieves better long-term survivals.

No abstract

The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factorlike domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumoros liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r ¼ 0.6594, Po0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.

Multiple bile duct hamartomas (BDHs)/von Meyenburg complexes, are tumor-like lesions of the liver. Malignant transformation in BDHs has been previously reported in very rare instances, and the most common tumor arising in this clinical setting is cholangiocarcinoma. Herein, we report on clinicopathological findings in two cases of cholangiocarcinoma occurring in liver with multiple BDHs. Histopathologically, multiple BDHs showed morphologic transition from clearly benign to dysplasia or carcinoma in situ, then to invasive carcinoma sequence of the biliary epithelium. The neoplastic epithelium showed positivity for cytokeratin 19, CA 19-9, and epithelial membrane antigen. Staining for Hep Par 1, alpha-fetoprotein, cytokeratin 20, and alpha1-antitrypsin was negative. All sections from the non-neoplastic liver in each specimen showed multiple BDHs. Any other clinically detectable primary tumor was not found. These two neoplasms were interpreted as a cholangiocarcinoma arising in BDHs. This suggested BDHs might be a risk factor of development of cholangiocarcinoma.

Frequent microsatellite alterations exist in HCC. LOH, which represents a tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis. MSI, which represents a mismatch repair gene pathway, is a rare event during liver carcinogenesis. Furthermore, LOH on certain chromosome regions may be correlated with clinicopathological characteristics in HCC.