Global DNA Methylation in Precancerous and Cancerous Lesions of the Uterine Cervix

Introduction: Persistent human papillomavirus (HPV) infection is the primary causal agent in the development of the uterine cervix carcinoma. Nevertheless, only a minority of high-risk HPV-associated lesions progress to cervical cancer, suggesting involvement of other molecular alterations. Among putative changes, aberrant methylation might be a crucial event. Design: Paraffin-embedded samples of benign lesions, cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinomas (SCC) were analyzed for DNA 5-methylcytosine content by immunohistochemistry with anti-5-methylcytosine antibodies and by high-performance liquid capillary electrophoresis (HPCE). Results: No significant difference of DNA 5-methylcytosine content was observed between normal tissues, benign lesions, low-grade lesions and high-grade lesions (p=0.6). In contrast, DNAs extracted from invasive SCC were hypomethylated when compared with normal and preneoplastic lesions (p=0.0004). An association between global DNA hypomethylation and the SCC stage was confirmed by HPCE. Conclusions: The transition from CIN lesions to invasive carcinoma seems to be closely linked to global DNA hypomethylation, which could be a useful marker of invasive uterine cervical lesions.