Hepatocellular carcinoma: Diagnosis and treatment

Befeler, Alex S.; Bisceglie, Adrian M. Di

doi:10.1053/gast.2002.33411

Cited by 525 publications

(386 citation statements)

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“…19,20 Risk factors include cirrhosis, hepatitis B and C infections, alcohol abuse, aflatoxin exposure, hemochromatosis, and alpha-1-antitrypsin deficiency. 19,21 The only definitive treatment is surgical resection or transplantation, 19,20 although over half the patients have disease recurrence after surgical resection. 19 Attempts have been made to identify markers that can predict disease recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…19 Attempts have been made to identify markers that can predict disease recurrence. Poor clinicopathologic prognostic factors include TNM staging (size, multiplicity, nodal status, metastasis, microvascular invasion) 18,20 and nuclear grade and microvascular invasion. 22 Survivin expression, nuclear in distribution by immunohistochemistry, and/or by RT-PCR is reported to be associated with unfavorable histology and aggressive disseminated disease in endometrial and ovarian carcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

et al. 2004

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Survivin is a novel inhibitor of apoptosis. It is detected in fetal and neoplastic adult tissue, but not in normal tissues. Several recent studies have shown that survivin not only inhibits apoptosis, but also accelerates cancer cell proliferative activity. Expression of the protein may be of prognostic significance and therapeutic relevance in many cancers. We investigated survivin expression in hepatocellular carcinoma, correlating results with proliferation (MIB-1), prognostic factors, and outcome. Paraffin-embedded sections of 72 hepatocellular carcinoma were immunostained for survivin and MIB-1 using tissue microarray technology. Expression was evaluated in nuclei and cytoplasm as intensity (0-3 þ ), and percentage of positive cells scored on a four-tiered system with less than 10% ¼ negative; 10-25% ¼ 1; 26-50% ¼ 2; 51-75% ¼ 3; and 76-100% ¼ 4. Frequency of nuclear survivin expression was 43%. There was a significant correlation between nuclear survivin expression and nuclear grade (P ¼ 0.0271), microvascular invasion (P ¼ 0.0064), mitotic rate (P ¼ 0.0017), and MIB-1 (P ¼ 0.0001), as well as local recurrence (P ¼ 0.0487), and disease-free survival (P ¼ 0.0098). Histologic grade (P ¼ 0.0544) and stage (P ¼ 0.0548) tended to correlate with survivin expression, which did not correlate with cirrhosis, tumor necrosis, multiple tumors, metastatic disease, or overall survival. Survivin expression correlates with poor prognostic parameters (high nuclear and histologic grade, microvascular invasion, increased proliferation (mitotic count, MIB-1)), local recurrence, and shorter diseasefree survival, but does not correlate with overall survival. An important role is suggested for survivin in progression, recurrence, and treatment of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

et al. 2004

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“…Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is a major cause of death in many countries (Befeler and Di Bisceglie, 2002). Chronic infections with hepatitis B (HBV) and C (HCV) viruses, high alcohol consumption and exposure to aflatoxin B1 are the main risk factors for HCC.…”

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confidence: 99%

Differential effects of inactivated Axin1 and activated β-catenin mutations in human hepatocellular carcinomas

et al. 2006

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Perturbations to the Wnt signaling pathway have been implicated in a large proportion of human hepatocellular carcinomas (HCCs). Activating b-catenin mutations and loss of function mutations in Axin1 are thought to be functionally equivalent. We examined the Wnt pathway in HCC by comparing the expression of b-catenin target genes and the level of b-catenin-dependent transcriptional activation, in 45 HCC tumors and four cell lines. Among these samples, b-catenin and AXIN1 were mutated in 20 and seven cases, respectively. We found a significant correlation between activated b-catenin mutations and overexpression of mRNA for the target genes glutamine synthetase (GS), G-protein-coupled receptor (GPR)49 and glutamate transporter (GLT)-1 (P ¼ 0.0001), but not for the genes ornithine aminotransferase, LECT2, c-myc and cyclin D1. We also showed that GS is a good immunohistochemical marker of b-catenin activation in HCC. However, we observed no induction of GS, GPR49 or GLT-1 in the five inactivated Axin1 tumors. b-Catenin-dependent transcriptional activation in two Axin1-mutated HCC cell lines was much weaker than in b-catenin-mutated cell lines. Our results strongly suggest that in HCC, contrary to expectation, the loss of function of Axin1 is not equivalent to the gain of function of b-catenin. Our results also suggest that the tumor suppressor function of Axin1 in HCC may be related to another, non-Wnt pathway.

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“…Hepatocellular carcinoma (HCC) is a highly fatal malignant neoplasm, with the majority of cases occurring in chronic hepatitis B virus (HBV) carriers (Befeler and Di Bisceglie, 2002;Wands, 2004). The HCC risk is 20-fold higher for individuals who are seropositive for HBV surface antigen (HBsAg) than for those who are HBsAg-seronegative (Yu and Chen, 1994).…”

Section: Introductionmentioning

confidence: 99%

Localization of a susceptibility locus for hepatocellular carcinoma to chromosome 4q in a hepatitis B hyperendemic area

Shih

et al. 2006

Oncogene

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Chromosome 4q is one of the most common regions with a high frequency of allelic loss in hepatocellular carcinoma (HCC). To identify the HCC-susceptibility locus on chromosome 4q, we have performed linkage and familybased association analyses on Chinese families with HCC from Taiwan, where hepatitis B is hyperendemic. Using 77 microsatellite markers spanning chromosome 4q on 52 multiplex families, we found suggestive evidence of linkage to 4q22.3-28.1 with a maximum two-point heterogeneity LOD (HLOD) score of 2.55 at marker D4S3240 on chromosome 4q25. Multipoint analyses with microsatellite markers in the region 4q22.3-28.1 resulted in a maximum HLOD score of 3.12 and a maximum nonparametric linkage (NPL) Z score of 1.98 (pointwise P ¼ 0.0080; region-wide empirical P ¼ 0.021) for D4S3240. The evidence for linkage to D4S3240 was seen mostly in a subset of 28 families lacking affected parents, which showed multipoint HLOD and NPL scores of 3.25 and 2.79 (pointwise P ¼ 0.0028; region-wide empirical P ¼ 0.008), respectively. Family-based association analyses of the 77 microsatellite markers in 191 families (53 multiplex plus 138 singleton families) using the pedigree disequilibrium test provide further support for observed linkage. Additional genotyping in the 52 multiplex families informative for linkage analyses was performed for 29 single-nucleotide polymorphisms around D4S3240. A common haplotype (at markers rs7442180 and rs221330) positioned B873 kb away from D4S3240 was associated with HCC, with P ¼ 0.0074.

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Hepatocellular carcinoma: Diagnosis and treatment

Cited by 525 publications

References 50 publications

Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome

Differential effects of inactivated Axin1 and activated β-catenin mutations in human hepatocellular carcinomas

Localization of a susceptibility locus for hepatocellular carcinoma to chromosome 4q in a hepatitis B hyperendemic area

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