Document Detail


CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes increase proportional to degree and duration of underlying cervical disease.
MedLine Citation:
PMID:  23456988     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Combined detection of CADM1 and MAL promoter methylation in cervical scrapes is a promising triage strategy for hrHPV-positive women. Here, CADM1 and MAL DNA methylation levels were analysed in cervical scrapes of hrHPV-positive women with no underlying high-grade disease, high-grade CIN and cervical cancer. CADM1 and MAL methylation levels in scrapes were firstly related to CIN-grade of the corresponding biopsy and secondly to CIN-grade stratified by the presence of 'normal' or 'abnormal' cytology as present in the accompanying scrape preceding the cervical biopsy. The scrapes included 167 women with ≤CIN1, 54 with CIN2/3 and 44 with carcinoma. In a separate series of hrHPV-positive scrapes of women with cervical intraepithelial neoplasia grade 2/3 (CIN2/3) (n=48), methylation levels were related to duration of preceding hrHPV infection (PHI; <5 and ≥5 years). Methylation levels were determined by quantitative methylation-specific PCR and normal cytology scrapes of hrHPV-positive women with histologically ≤CIN1 served as reference. CADM1 and MAL methylation levels increased proportional to severity of the underlying lesion, showing an increase of 5.3- and 6.2-fold in CIN2/3, respectively, and 143.5- and 454.9-fold in carcinomas, respectively, compared to the reference. Methylation levels were also elevated in CIN2/3 with a longer duration of PHI (i.e. 11.5- and 13.6-fold, respectively). Moreover, per histological category, methylation levels were higher in accompanying scrapes with abnormal cytology than in scrapes with normal cytology. Concluding, CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes are related to the degree and duration of underlying cervical disease and markedly increased in cervical cancer. © 2013 Wiley Periodicals, Inc.
Authors:
Mariska Bierkens; Albertus T Hesselink; Chris J L M Meijer; Daniëlle A M Heideman; G Bea A Wisman; Ate G J van der Zee; Peter J F Snijders; Renske D M Steenbergen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-2
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 UICC.
Affiliation:
Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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