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Association between dense CADM1 promoter methylation and reduced protein expression in high-grade CIN and cervical

R M Overmeer1, F E Henken, P J F Snijders

  • 1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.

The Journal of Pathology
|May 24, 2008
PubMed

Insights

Cell adhesion molecule 1 (CADM1) promoter methylation increases with cervical lesion severity. Dense methylation is a promising biomarker for identifying women at high risk of cervical cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gynecology

Background:

  • TSLC1, now known as CADM1, is implicated in high-risk HPV-mediated cervical carcinogenesis.
  • CADM1 silencing is frequently caused by promoter methylation.

Purpose of the Study:

  • To assess CADM1 promoter methylation in cervical lesions.
  • To correlate methylation with anchorage-independent growth and gene silencing.
  • To identify a CADM1-based methylation marker for cervical cancer risk stratification.

Main Methods:

  • Methylation-specific PCR on cell lines, PBMCs, and cervical samples (normal to malignant).
  • Immunohistochemistry to analyze CADM1 protein expression in cervical tissues.
  • Statistical analysis of methylation density, disease severity, and protein expression.

Main Results:

  • Methylation density correlated with anchorage-independent growth and CADM1 gene silencing.
  • Methylation frequency and density increased with cervical lesion severity.
  • Dense methylation (>or= 2 regions) rose from 5% in normal samples to 83% in squamous cell carcinomas (SCCs), significantly decreasing CADM1 expression.
  • Dense methylation was significantly higher in CIN3+ lesions and SCCs compared to adenocarcinomas.

Conclusions:

  • Dense CADM1 promoter methylation is significantly associated with cervical carcinogenesis.
  • CADM1 promoter methylation serves as a potential biomarker for identifying high-risk HPV-positive women.
  • This marker can aid in assembling a panel for triaging women at risk of CIN3+.

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