TIMP-2 gene methylation in cervical precursor and invasive lesions

• Published in: Experimental and molecular pathology 2015-02, Vol.98 (1), p.119-123
• Main Authors: Furtado, Yara, Almeida, Gutemberg, Silveira, Filomena Aste, Silva, Kátia S., Maldonado, Paula, do Val, Isabel Cristina, Cavalcanti, Silvia, L, Miranda-Alves, da Costa Carvalho, Maria da Gloria
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Cervix; Cross-Sectional Studies; DNA Methylation; DNA, Viral - genetics; Female; Follow-Up Studies; Humans; Methylation; Middle Aged; Neoplasia; Neoplasm Invasiveness; Papillomaviridae - genetics; Papillomavirus infection; Papillomavirus Infections - genetics; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Polymerase Chain Reaction; Prognosis; TIMP-2; Tissue Inhibitor of Metalloproteinase-2 - genetics; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2015.01.008

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. 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. 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). 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. •Presence of TIMP-2 gene methylation in intraepithelial and invasive lesions of cervix uteri•Association between TIMP-2 gene methylation and the presence of DNA-HPV in cervix samples•Association between TIMP-2 gene methylation and clinical evolution of cervical lesions