Expressão do fator inibitório da migração de macrófagos e do fator de permeabilidade vascular em lesões da cérvice uterina induzidas pelo papilomavírus humano

Abstract

The cervical cancer is the third most frequent type of cancer in women in Brazil, and its frequency is only lower than those observed for non-melanoma skin cancer and breast cancer. Macrophage migration inhibitory factor (MIF) is produced by different cell types and participates in a complex chain of events that favors the process of carcinogenesis, being possible to observe a high expression level in almost all types of human cancer, such as in cervical cancer. MIF also induces a dose-dependent increase in the excretion of vascular endothelial growth factor (VEGF), which promotes angiogenesis, tumor growth and migration of these cells in cervical cancer. The objective of this study was to investigate the expression of MIF and VEGF in patients with or without cervical lesions, in order to identify the existence of a direct relationship between the presence of those markers with the degree of the lesion of the patient, as well, as with the presence of human papillomavirus (HPV). The study included 45 women who had been referred to the Maternity School Januário Cicco with suspected lesions of the uterine cervix. Patients who accepted to participate in the study answered a questionnaire to obtain socio-demographic data, followed by clinical examination. Patients who agreed to participate in the study answered a questionnaire to obtain socio-demographic data, followed by clinical examination. Two cervix tissue fragments were collected from the women who underwent colposcopy, one for histopathological analysis and the other for HPV detection by conventional PCR. The expression of the biomarkers, MIF and VEGF, was detected by the immunohistochemical technique. The positive area of each biomarker was read and quantified using the ImageJ® program and the result was analyzed using the statistical program SPSS® Statistics and GraphPad Prism. Of the 45 patients included in the study, 20% showed no lesions, while 80% had some type of alteration in the exam; being 35.55% low-grade squamous intraepithelial lesion (LSIL) type and 44.44% highgrade squamous intraepithelial lesion (HSIL) type. The overall prevalence rate of genital HPV infection was 80%, with 86.1% in patients with lesions. Mean VEGF and MIF expression increased gradually when compared to normal patients, LSIL and HSIL, respectively, corresponding to the following values: 19.62, 41.59 and 55.42 for VEGF and 4.36, 9, 44 and 22.86 for MIF. A positive correlation between MIF and VEGF expression was found (r = 0.523, p = <0.001). Through this work it was concluded that VEGF and MIF are correlated and involved in the cervical dysplasia process, increasing its expression as the lesion progresses. However, it was not possible to find an association between the presence of HPV and the levels of MIF and VEGF.