Express?o do fator inibit?rio da migra??o de macr?fagos e do fator de permeabilidade vascular em les?es da c?rvice uterina induzidas pelo papilomav?rus humano

Autor: Nobre, Camila Cristina Guimar?es
Jazyk: portugalština
Rok vydání: 2017
Předmět:
Zdroj: Repositório Institucional da UFRNUniversidade Federal do Rio Grande do NorteUFRN.
Druh dokumentu: masterThesis
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)
O c?ncer do colo do ?tero ? o terceiro tipo de c?ncer mais frequente em mulheres no Brasil, sendo a sua frequ?ncia menor apenas do que aquelas observadas para o c?ncer de pele n?o-melanoma e c?ncer de mama. O fator inibit?rio da migra??o de macr?fagos (MIF) ? produzido por diferentes tipos de c?lulas e participa de uma cadeia complexa de eventos que favorece o processo de carcinog?nese, sendo poss?vel observar um alto n?vel de express?o em quase todos os tipos de c?ncer humano, entre eles o c?ncer do colo do ?tero. O MIF tamb?m induz um aumento dose dependente na excre??o do fator de crescimento de endot?lio vascular (VEGF), que promove a angiog?nese, o crescimento tumoral e a migra??o dessas c?lulas no c?ncer do colo do ?tero. O objetivo deste estudo foi investigar a express?o de MIF e VEGF em pacientes que apresentam ou n?o les?es do colo do ?tero, no intuito de identificar a exist?ncia de uma rela??o direta entre a presen?a dos marcadores MIF e VEGF com o grau da les?o da paciente, bem como, com a presen?a do papilomav?rus humano (HPV). Foram inclu?das no estudo 45 mulheres que haviam sido encaminhadas para a Maternidade Escola Janu?rio Cicco com suspeita de les?es na c?rvice uterina. As pacientes que aceitaram participar do estudo responderam a um question?rio, para obten??o de dados s?cio-demograficos, seguido de exame cl?nico. Das mulheres que se submeteram a colposcopia, foram coletados dois fragmentos de tecido do colo do ?tero, um para an?lise histopatol?gica e outro para detec??o do HPV por PCR convencional. A express?o dos biomarcadores, MIF e VEGF, foi detectada pela t?cnica de imuno-histoqu?mica. A ?rea positiva de cada biomarcador foi lida e quantificada utilizando o programa ImageJ?, e o resultado foi analisado atrav?s dos programas de estat?stica SPSS? Statistics e GraphPad Prism. Das 45 pacientes inclu?das no estudo, 20% apresentaram resultado do exame dentro dos padr?es da normalidade, enquanto que 80% apresentaram algum tipo de altera??o no exame; sendo 35,55% les?es intraepiteliais de baixo grau (LIEBG) e 44,44% les?es intraepiteliais de alto grau (LIEAG). A taxa de preval?ncia global de infec??o genital pelo HPV foi de 80%, sendo 86,1% em pacientes com les?o. A express?o m?dia do VEGF e do MIF tiveram um aumento gradativo quando comparado entre as pacientes normais, LIEBG e LIEAG, correspondendo respectivamente aos seguintes valores, 19,62, 41,59 e 55,42 para o VEGF e 4,36, 9,44 e 22,86 para MIF. Foi poss?vel verificar uma correla??o positiva entre a express?o de MIF e VEGF (r = 0,523, p =
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 Janu?rio 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 =
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