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 developmentof the uterine cervix carcinoma. Nevertheless, only a minority of high-risk HPV-associated lesions progressto cervical cancer, suggesting involvement of other molecular alterations. Among putative changes, aberrantmethylation might be a crucial event. Design: Paraffin-embedded samples of benign lesions, cervical intraepithelialneoplasia (CIN) and invasive squamous cell carcinomas (SCC) were analyzed for DNA 5-methylcytosine contentby immunohistochemistry with anti-5-methylcytosine antibodies and by high-performance liquid capillaryelectrophoresis (HPCE).
Results: No significant difference of DNA 5-methylcytosine content was observed betweennormal tissues, benign lesions, low-grade lesions and high-grade lesions (p=0.6). In contrast, DNAs extractedfrom invasive SCC were hypomethylated when compared with normal and preneoplastic lesions (p=0.0004). Anassociation between global DNA hypomethylation and the SCC stage was confirmed by HPCE.
Conclusions: Thetransition 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.