Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease.
Clin Cancer Res
; 9(5): 1773-8, 2003 May.
Article
em En
| MEDLINE
| ID: mdl-12738733
ABSTRACT
PURPOSE:
There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. EXPERIMENTALDESIGN:
In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled.RESULTS:
Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease.CONCLUSIONS:
This study demonstrates (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
/
Regiões Promotoras Genéticas
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Colangiocarcinoma
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Metilação de DNA
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Inibidor p16 de Quinase Dependente de Ciclina
/
Proteína Supressora de Tumor p14ARF
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article