Altered expression of E-cadherin in hepatocellular carcinoma: correlations with genetic alterations, beta-catenin expression, and clinical features. Hepatology (Baltimore, Md.) [Hepatology] Journal article | | Title | Altered expression of E-cadherin in hepatocellular carcinoma: correlations with genetic alterations, beta-catenin expression, and clinical features. | | Author(s) | Wei Y, Van Nhieu JT, Prigent S, Srivatanakul P, Tiollais P, Buendia MA | | Institution | Unité de Recombinaison et Expression Génétique (Inserm U163), Institut Pasteur, Paris, France. | | Source | Hepatology 2002 Sep; 36(3):692-701. | | MeSH | Adolescent
Adult
Aged
Cadherins
Carcinoma, Hepatocellular
Chromosome Mapping
Chromosomes, Human, Pair 16
Cytoskeletal Proteins
DNA Methylation
DNA Mutational Analysis
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Liver
Liver Neoplasms
Loss of Heterozygosity
Male
Middle Aged
Promoter Regions (Genetics)
Research Support, Non-U.S. Gov't
Trans-Activators
beta Catenin
| | Abstract | E-cadherin is a key cell adhesion protein implicated as a tumor/invasion suppressor in human carcinomas and a binding partner of beta-catenin, which plays a critical role in Wnt signaling and in tumorigenesis. Here we report genetic and expression studies of E-cadherin and beta-catenin in hepatocellular carcinoma (HCC). Immunohistochemical analysis of E-cadherin expression in 37 HCCs and adjacent nontumor tissues revealed important variations among tumor samples, ranging from complete or heterogeneous down-regulation in 35% of cases to marked overexpression in 40% of tumors. Loss of E-cadherin expression was closely associated with loss of heterozygosity (LOH) at the E-cadherin locus and methylation of CpG islands in the promoter region (P <.002), predominantly in hepatitis B virus (HBV)-related tumors (P <.005). No mutation of the E-cadherin gene could be detected in the tumors examined, suggesting the requirement for reversible mechanisms of E-cadherin down-regulation. In most HCCs, including E-cadherin-positive and -negative cases, beta-catenin was strongly expressed at the cell membrane and nuclear accumulation of the protein was correlated with the presence of mutations in the beta-catenin gene itself, but not with E-cadherin loss. At difference with a number of epithelial cancers, vascular invasion was frequently noted in HCCs showing enforced expression of the membranous E-cadherin/beta-catenin complex. In conclusion, these data support the notion that E-cadherin might play diverse and seemingly paradoxic roles in HCC, reflecting specific requirements for tumor growth and spread in the liver environment. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 12198663 |
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