Claudia Teixeira da Costa Lodi1, Márcia Antoniazi Michelin2, Maria Inês Miranda Lima3, Eddie Fernando Candido Murta2, Letícia da Conceição Braga4, Leticia Montes5, Victor Hugo Melo6. 1. Medical Science School of Minas Gerais, Belo Horizonte, MG, Brazil. claudiatclodi@gmail.com. 2. Research Institute of Oncology, Federal University of Triangulo Mineiro, Uberaba, Brazil. 3. Gynecologist at Santa Casa Belo Horizonte, Belo Horizonte, Brazil. 4. Cell Biology Laboratory of Research and Development Management of Ezequiel Dias Foundation, Belo Horizonte, Brazil. 5. Biomedical of Research Institute of Oncology, Federal University of Triangulo Mineiro, Uberaba, Brazil. 6. School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Abstract
PURPOSE: Aberrant DNA methylation is present in virtually all types of human cancer. There is no clear evidence that methylation status can predict bad prognosis in patients with CIN recurrence in HIV infected. This study evaluates the relationship between aberrant methylation of CpG islands of CDH1, TIMP3 and MGMT genes and CIN recurrence in HIV-infected and -noninfected women. METHODS: This is a nested case-control study involving 33 cases with CIN recurrence and 114 controls without recurrence, HIV infected and noninfected, treated with LEEP, between 1999 and 2004. Recurrence diagnosis was established after biopsy. Genes methylation profile was assessed by MSP-PCR technique in formalin-fixed, paraffin-embedded cone specimens. Statistical analysis was performed to compare categorical variables, using χ2 test with Yates correction and Fisher's exact test. Multivariate analysis was carried out using logistic regression. RESULTS: CIN recurrence was more frequent in women with glandular involvement (OR 11.6; 95% CI 2.93-45.89) and compromised surgical margins (OR 2.5; 95% CI 0.87-7.27) in the cervical cone and in HIV-infected women (OR 2.47; 95% CI 0.87-7.05). One methylated allele of CDH1, TIMP3 and MGMT genes was present in 87.9% women with CIN recurrence. Promoter hypermethylation of TIMP3 and MGMT was detected in women with CIN recurrence and without CIN recurrence independent of HIV infection with significant difference between groups (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.
PURPOSE: Aberrant DNA methylation is present in virtually all types of humancancer. There is no clear evidence that methylation status can predict bad prognosis in patients with CIN recurrence in HIV infected. This study evaluates the relationship between aberrant methylation of CpG islands of CDH1, TIMP3 and MGMT genes and CIN recurrence in HIV-infected and -noninfected women. METHODS: This is a nested case-control study involving 33 cases with CIN recurrence and 114 controls without recurrence, HIV infected and noninfected, treated with LEEP, between 1999 and 2004. Recurrence diagnosis was established after biopsy. Genes methylation profile was assessed by MSP-PCR technique in formalin-fixed, paraffin-embedded cone specimens. Statistical analysis was performed to compare categorical variables, using χ2 test with Yates correction and Fisher's exact test. Multivariate analysis was carried out using logistic regression. RESULTS:CIN recurrence was more frequent in women with glandular involvement (OR 11.6; 95% CI 2.93-45.89) and compromised surgical margins (OR 2.5; 95% CI 0.87-7.27) in the cervical cone and in HIV-infectedwomen (OR 2.47; 95% CI 0.87-7.05). One methylated allele of CDH1, TIMP3 and MGMT genes was present in 87.9% women with CIN recurrence. Promoter hypermethylation of TIMP3 and MGMT was detected in women with CIN recurrence and without CIN recurrence independent of HIV infection with significant difference between groups (p = 0.04 and p = 0.02, respectively). CONCLUSIONS:CIN recurrence was associated with glandular involvement and compromised margins in cone biopsy and HIV infection. The presence of CpG islands hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN recurrence.
Entities:
Keywords:
Cervical intraepithelial neoplasia; DNA methylation; Human immunodeficiency virus; Human papillomavirus; Loop electrosurgical excision procedure; Recurrence
Authors: Wieke W Kremer; Marjolein van Zummeren; Erika Breytenbach; Karin L Richter; Renske D M Steenbergen; Chris J L M Meijer; Greta Dreyer Journal: AIDS Date: 2019-11-01 Impact factor: 4.177