TIMP-2 gene methylation in cervical precursor and invasive lesions

Abstract

Objective: To analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions.

Methods: Cross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed.

Results: TIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19).

Conclusion: TIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.

Keywords: Cervix; Methylation; Neoplasia; Papillomavirus infection; TIMP-2.