Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis
| Autor: | G G, Chung, E, Provost, E P, Kielhorn, L A, Charette, B L, Smith, D L, Rimm |
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| Rok vydání: | 2001 |
| Předmět: |
Cell Nucleus
Cytoplasm Reproducibility of Results Cadherins Phosphoproteins Prognosis Transfection Immunohistochemistry Recombinant Proteins Cell Line Gene Expression Regulation Neoplastic Survival Rate Cytoskeletal Proteins Dogs Treatment Outcome Trans-Activators Animals Humans Colorectal Neoplasms beta Catenin Neoplasm Staging Oligonucleotide Array Sequence Analysis Proportional Hazards Models |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 7(12) |
| ISSN: | 1078-0432 |
| Popis: | Beta-catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of beta-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene, is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression pattern of beta-catenin and phosphospecific beta-catenin was correlated with clinical outcome in a series of patients with colorectal cancer.Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression and subcellular localization of beta-catenin and phosphospecific beta-catenin. These results were correlated with other clinicopathological factors and with overall survival.The majority of cancers retained some degree of beta-catenin membranous staining, whereas cytoplasmic or nuclear expression was seen in 42.5% and 20.4% of specimens, respectively. Phospho-beta-catenin showed nuclear staining in 9.5% of specimens, and there was no apparent membranous or cytoplasmic staining. There was no significant association between beta-catenin or phospho-beta-catenin and grade or stage. However, there was a positive correlation between beta-catenin and phospho-beta-catenin (P = 0.039), with phospho-beta-catenin representing a subset of nuclear beta-catenin. Patients with nuclear expression of beta-catenin did not have an altered survival compared with those that did not (P = 0.5611). Nuclear expression of phospho-beta-catenin, however, was associated with an improved survival (P = 0.0006). In multivariate analysis, only stage and phospho-beta-catenin were independently predictive of overall survival (P0.001 and P = 0.0034, respectively).These findings support a role for beta-catenin overexpression in colorectal tumorigenesis and provide initial evidence that phospho-beta-catenin may be a marker for improved overall survival independent of stage and grade. |
| Databáze: | OpenAIRE |
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