Low microsatellite instability is associated with poor prognosis in stage C colon cancer.
J Clin Oncol
; 23(10): 2318-24, 2005 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-15800322
PURPOSE: The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O(6)-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. PATIENTS AND METHODS: The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation. RESULTS: We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. CONCLUSION: MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias del Colon
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Repeticiones de Microsatélite
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O(6)-Metilguanina-ADN Metiltransferasa
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Inestabilidad Genómica
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Oncol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Estados Unidos