Clinicopathological Features Of Hepatocellular Carcinoma Patients Research Articles

Pharmacological Unmasking Microarray Approach-Based Discovery of Novel DNA Methylation Markers for Hepatocellular Carcinoma

DNA methylation is one of the main epigenetic mechanisms and hypermethylation of CpG islands at tumor suppressor genes switches off these genes. To find novel DNA methylation markers in hepatocellular carcinoma (HCC), we performed pharmacological unmasking (treatment with 5-aza-2'-deoxycytidine or trichostatin A) followed by microarray analysis in HCC cell lines. Of the 239 promoter CpG island loci hypermethylated in HCC cell lines (as revealed by methylation-specific PCR), 221 loci were found to be hypermethylated in HCC or nonneoplastic liver tissues. Thirty-three loci showed a 20% higher methylation frequency in tumors than in adjacent nonneoplastic tissues. Correlation of individual cancer-related methylation markers with clinicopathological features of HCC patients (n = 95) revealed that the number of hypermethylated genes in HCC tumors was higher in older than in younger patients. Univariate and multivariate survival analysis revealed that the HIST1H2AE methylation status is closely correlated with the patient's overall survival (P = 0.022 and P = 0.010, respectively). In conclusion, we identified 221 novel DNA methylation markers for HCC. One promising prognostic marker, HIST1H2AE, should be further validated in the prognostication of HCC patients.

957 THE CLINICAL SIGNIFICANCE OF PLASMA OSTEOPONTIN LEVEL IN EGYPTIAN PATIENTS WITH HEPATITIS C VIRUS-RELATED HEPATOCELLULAR CARCINOMA

Background and Aims. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide. Osteopontin (OPN) is a secreted glycoprotein frequently associated with various tumors. This study aimed to investigate the clinical usefulness of plasma OPN level as a biomarker for HCC among high-risk patients compared to alpha-fetoprotein (AFP) and to evaluate its relationship with clinicopathological features of HCC patients. Methods. Plasma levels of OPN and AFP were measured in 60 Egyptian patients with hepatitis C virus-related liver cirrhosis (30 with HCC, 30 without HCC) and 20 healthy controls. Results. Plasma OPN levels in cirrhotic patients with HCC were significantly higher than in those without HCC and controls (p !0.001). Among HCC patients, plasma levels of OPN increased significantly with advanced Child-Pugh class (BeC, p !0.001), late tumor stage (IIIeIV, p !0.001), larger tumor size ($5 cm, p !0.01), and high tumor grade (p !0.01). The sensitivity and specificity of OPN for HCC were 88.3% and 85.6%, respectively, at a cut-off value of 9.3 ng/mL. OPN had a greater area under curve value (0.918) than AFP (0.712), suggesting superior diagnostic accuracy of OPN. Moreover, no significant correlation was found between OPN and AFP levels in HCC patients. Conclusions. Plasma OPN can be regarded as a promising diagnostic biomarker for HCC in the surveillance of Egyptian patients with HCV infection. It could also serve as an adverse prognostic factor for HCV-related HCC patients. 2010 IMSS. Published by Elsevier Inc.

Prognosis of hepatocellular carcinoma with biliary tumor thrombi after liver surgery

The incidence of biliary tumor thrombi (BTT) in hepatocellular carcinoma (HCC) is very low and operative outcomes are poor. There is little information on the postoperative prognostic factors for patients with HCC with BTT. We analyzed retrospectively the clinicopathologic features of 22 patients with HCC with BTT to identify the prognostic factors associated with operative outcome. Of the 551 patients who underwent hepatic resection for HCC between 1988 and 2007, 22 (4.0%) had HCC with BTT. Their clinicopathologic features were compared with those with HCC but no BTT. The survival rates were also calculated for various clinicopathologic factors. Of the 22 patients, 13 (59%) also had portal or hepatic vein tumor thrombosis. Multiple HCC tumors were identified in 91% of patients and 20 patients were classified as stage IVA. The 1- and 3-year overall survival rates were 89% and 73% for patients with HCC free of BTT, respectively, and 62% and 30%, respectively, for those of HCC with BTT (P < .0001). Portal or hepatic vein tumor thrombosis was the only significant determinant of poor prognosis in 22 patients with HCC with BTT. The 1- and 3-year cumulative survival rates were 89% and 52%, respectively, for patients with only BTT but worse in those of HCC with both BTT and portal or hepatic vein tumor thrombosis (43% and 17%, respectively). The clinicopathologic features of HCC patients with BTT indicated advanced-stage disease and poor operative outcomes. Portal or hepatic vein tumor thrombosis was the only significant determinant of poor prognosis of HCC patients with BTT.

Expression of vascular endothelial‐cadherin in human hepatocellular carcinoma tissues

Angiogenesis is important in tumor growth and progression to metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific cadherin required for angiogenesis, but its expression in hepatocellular carcinoma (HCC) tissues has not been examined. Expression of VE-cadherin was analyzed in 31 HCC frozen tissue specimens by immunohistochemical and immunoelectron microscopic procedures. In addition, the association of its expression with clinicopathological parameters was investigated to determine the possible diagnostic or predictive value of VE-cadherin expression in neoplastic and non-neoplastic liver lesions. Immunoreactive VE-cadherin expression was faint or barely detectable on sinusoidal endothelial cells of normal liver but was evident on sinusoidal or capillary endothelium of chronic hepatitis, cirrhosis, and HCC tissues. VE-cadherin expression was more intense on capillary endothelium of HCC tissues in 26 (84%) of 31 patients than on sinusoidal endothelium of surrounding non-tumorous liver tissues with chronic liver diseases. The intensity or intracapillary extent of positive stain for VE-cadherin on capillary endothelium of HCC tissues was significantly associated with tumor size, capsular invasion and tumor cell differentiation in HCC. Intense VE-cadherin expression was evident in capillary endothelium of HCC tissues, giving the first indication of association with clinicopathological features of HCC patients.