Análise da expressão do TNF-α, β-Defensinas 2 e 3 e proteína p16 na mucosa anal de pacientes infectados pelo Papilomavírus humano

Autor: NUNES, Maria Julliana Galvão
Jazyk: portugalština
Rok vydání: 2017
Předmět:
Zdroj: Repositório Institucional da UFPEUniversidade Federal de PernambucoUFPE.
Druh dokumentu: Doctoral Thesis
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A incidência de carcinoma anal e lesões precursoras relacionadas tem aumentado no mundo, em homens e mulheres e a infecção persistente pelo Papilomavírus humano (HPV) desempenha um papel fundamental na carcinogênese anal. Os fatores de risco para o desenvolvimento de câncer anal incluem intercurso anal, múltiplos parceiros e infecção cervical pelo HPV. Desta forma, o objetivo deste estudo foi avaliar a infecção simultânea pelo HPV na mucosa cervical e anal e elucidar a associação entre a expressão local da proteína p16, β-defensina-2 e 3 e TNF-α (fator de necrose tumoral alfa) na mucosa anal e o grau de lesões anais associadas ao HPV. O grupo de estudo foi constituído por mulheres sexualmente ativas, com idade entre 18 e 60 anos. A coleta de células foi realizada a partir da mucosa cervical e anal com escova ginecológica, seguida de exame de colposcopia e anuscopia. O DNA foi extraído de amostras de células anais e cervicais e a PCR convencional foi realizada para detectar presença de HPV (tipos: 6, 16, 18, 31 e 33). A PCR em tempo real foi realizada utilizando primers específicos para a β-defensina 2, 3 e TNF-α. Os fragmentos de biopsia foram submetidos a coloração hematoxilina-eosina de rotina para a avaliação histológica e reação imunohistoquímica utilizando anticorpo anti-p16. Neste estudo, a positividade para p16 foi associada ao grupo com neoplasia, estatisticamente significativo (p = 0,0002) e padrão contínuo foi predominante. Cerca de 75% dos pacientes com neoplasia foram positivos para HPV e p16. Verificou-se alta taxa de infecção por HPV nas mucosas anal (70,52%), cervical (74,73%) e infecção simultânea cervical e anal (54,73%). A infecção simultânea (mucosa anal e cervical) pelo mesmo tipo de HPV foi observada em 17,30% dos pacientes. Entre os tipos de HPV identificados, o genótipo predominante nas amostras anal e cervical foi HPV6 (26,38%) e (19,71%), respectivamente. Nossos resultados também mostraram uma diminuição da expressão de TNF-α em lesões anais de alto grau em comparação com o normal HPV-positivo (p
The incidence of anal carcinoma and related precursor lesions have been increasing worldwide for both men and women. The human papillomaviruses (HPVs) play a fundamental role in anal carcinogenesis, through persistent infection. Women with cervical cancer and history anal intercourse have an increased risk of anal cancer. The aim of this study was to evaluate simultaneous HPV infection in cervical and anal mucosa and to elucidate the association between p16 protein, β-defensin-2, 3 and TNF-α (tumor necrosis factor alpha) expression local in the anal mucosa and the degree of HPV-associated anal lesions. Study group was composed of sexually active immunocompetent women. Cells collection was performed from cervical and anal mucosa with a brush, followed by anuscopy and colposcopy exam. DNA was extracted from anal and cervical cell samples and PCR was performed to detect HPV presence (types: 6, 16, 18, 31 and 33). Real-time PCR was performed using specific primers to β-defensin 2, 3 and TNF-α. Biopsy fragments were subjected to routine hematoxylin-eosin staining for the histological assessment and immunohistochemistry reaction using anti-p16 antibody. In our study, positivity for p16 was frequently associated with group with neoplasia, statistically significant (P = 0.0002) and continuous pattern was predominant. About 75% of patients with neoplasia were positive for HPV and p16. A high rate of HPV infection in anal (70.52%), cervical (74.73%) and simultaneous cervical and anal mucosa (54.73%) was found. Simultaneous infection (anal and cervical mucosa) by the same type HPV was observed in 17.30% of the patients. Among all HPV types identified, the predominant genotype in anal and cervical samples was HPV6 (26.38%) and (19.71%), respectively. Our findings also showed a decreased TNF-α expression in high-grade anal lesion compared to normal HPV-positive (p < 0.0001), whereas expression levels of β-defensin 3 were increased in high-grade patients (p = 0.0009). The acquisition of simultaneous infection anal and cervical may occur by different means, showing that the anal canal is also a source of infection.
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