Prognostic role of beta-catenin and p53 expression in the metastatic progression of sporadic colorectal cancer.
Hum Pathol
; 41(6): 867-76, 2010 Jun.
Article
en En
| MEDLINE
| ID: mdl-20129645
ABSTRACT
Beta-catenin and p53 play key roles in tumorigenesis. The relationships between these 2 signaling pathways and their contribution to colorectal cancer metastatic progression have not been completely elucidated. We analyzed 141 cases of primary sporadic colorectal cancer, 45 matched metastases, and 80 samples of normal mucosa by immunohistochemistry on paraffin-embedded specimens. The expression profiles were also related to patients' clinicopathologic features and 5-year survival. In primary tumors, beta-catenin immunoreactivity was nuclear (27%), predominantly membrane/cytosolic (46.0%) or negative (27%). This latter subgroup was strongly related to microsatellite instability, in particular to MLH-1 deficiency. Remarkably, beta-catenin membrane/cytosolic expression in primary tumors was reduced in the corresponding matched metastases. p53 showed a significant increase in immunoreactivity in (66.7%), whereas it was negative in (33.3%) of tumors. When we considered the expression of both genes, the combination of negative beta-catenin and positive p53 nuclear staining (21%) was strongly related to a higher frequency of liver metastases. Such an association was significantly related to a worse prognosis than any other combination. In a multivariate analysis, beta-catenin and distant metastases were independent prognostic markers. We suggest that a combination of low beta-catenin and high p53 expression in primary colorectal cancers may be a prognostic factor in predicting the progression of the disease, the occurrence of metastasis, and a more severe outcome.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Biomarcadores de Tumor
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Proteína p53 Supresora de Tumor
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Beta Catenina
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hum Pathol
Asunto de la revista:
PATOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia