Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical SCC.
J Pathol
; 215(4): 388-97, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18498117
ABSTRACT
We previously showed that silencing of TSLC1, recently renamed CADM1, is functionally involved in high-risk HPV-mediated cervical carcinogenesis. CADM1 silencing often results from promoter methylation. Here, we determined the extent of CADM1 promoter methylation in cervical (pre)malignant lesions and its relation to anchorage-independent growth and gene silencing to select a CADM1-based methylation marker for identification of women at risk of cervical cancer. Methylation-specific PCRs targeting three regions within the CADM1 promoter were performed on high-risk HPV-containing cell lines, PBMCs, normal cervical smears, and (pre)malignant lesions. CADM1 protein expression in cervical tissues was analysed by immunohistochemistry. All statistical tests were two-sided. Density of methylation was associated with the degree of anchorage-independent growth and CADM1 gene silencing in vitro. In cervical squamous lesions, methylation frequency and density increased with severity of disease. Dense methylation (defined as >or= 2 methylated regions) increased from 5% in normal cervical samples to 30% in CIN3 lesions and 83% in squamous cell carcinomas (SCCs) and was significantly associated with decreased CADM1 protein expression (p < 0.00005). The frequency of dense methylation was significantly higher in >or= CIN3 compared with
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Inmunoglobulinas
/
Carcinoma de Células Escamosas
/
Biomarcadores de Tumor
/
Displasia del Cuello del Útero
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Neoplasias del Cuello Uterino
/
Regiones Promotoras Genéticas
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Proteínas Supresoras de Tumor
/
Proteínas de la Membrana
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
J Pathol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Países Bajos