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.