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Doctoral Thesis
DOI
https://doi.org/10.11606/T.25.2022.tde-08062022-104250
Document
Author
Full name
Aloizio Premoli Maciel
Institute/School/College
Knowledge Area
Date of Defense
Published
Bauru, 2021
Supervisor
Committee
Santos, Paulo Sergio da Silva (President)
Oliveira, Denise Tostes
Romão, Elen Almeida
Sarmento, Dmitry José de Santana
Title in Portuguese
Análise de biomarcadores bucais carcinogênicos em indivíduos com doença renal crônica receptores de transplante renal
Keywords in Portuguese
Biomarcadores tumorais
Carcinogênese
Neoplasias labiais
Queilite
Transplante de Rim
Abstract in Portuguese
Receptores de transplante renal (RTR) tem um risco de manifestação de carcinoma espinocelular (CEC) de lábio inferior de 4 a 46.6 vezes maior que a população normal. A queilite Actínica (QA) é uma lesão potencialmente maligna que antecede à manifestação do CEC de lábio e poder ser identificada através do exame clínico. Da mesma maneira, uma das formas de realizar a monitorização da carcinogênese em RTR, é através da análise de anomalias nucleares a nível celular, para poder prevenir e identificar precocemente o CEC de lábio inferior em RTR. Portanto, o objetivo deste estudo foi analisar a manifestação da QA e sua associação com a presença de anomalias nucleares nos RTR, para identificar biomarcadores na boca que se associem ao CEC de lábio inferior. Este estudo foi um estudo clínico-histopatológico, observacional, transversal com amostra por conveniência a través da avaliação clínica da QA e identificação histopatológica de anomalias nucleares da região do lábio inferior de RTR. A avaliação clínica foi realizada por um único examinador calibrado; a avaliação de alterações nucleares foi realizada por dois examinadores calibrados e cegados. Foram registradas informações do RTR como idade, sexo, cor de pele, tempo de diálise antes do transplante, tempo de transplante, imunossupressores, exposição a fatores de risco como etilismo, tabagismo, exposição solar e histórico de infecções virais. A avalição clínica foi realizada através de exame clínico e análise fotográfico do lábio inferior. Para a avaliação histopatológica, foram coletadas células do lábio inferior através de raspado tecidual e acondicionamento em vaios com metanol e corados por reação de Feulgen. As anomalias nucleares foram classificadas como micronúcleos, brotamento nuclear, ponte citoplasmático e binucleação. Para análise estatístico foram utilizados o teste exato de Fisher e Macnemar (p<0,05). A amostra foi de 48 RTR, com diagnóstico de QA em 29(60,41%). O estadiamento da QA foi associado a RTR leucodermas (p<0,05). A presença de QA foi associado ao histórico de exposição a agentes químicos voláteis etilismo e tabagismo (p<0,05); histórico de uso de tacrolimus, azatioprina e sirolimus (p<0,001). O estadiamento da QA foi associado ao uso de Micofenolato (p<0,05). A administração de menores doses de Sirolimus foi associado a grau III e IV de QA (p<0,05). Infecções por Epstein-Barr Vírus e Herpes Vírus Simples foram associados a presença da QA (p<0,05). Entre as anomalias nucleares, a binucleação celular foi associada a RTR com mais de 7 anos de TxR (p=0,008). Todas as anomalias nucleares foram associadas ao uso de tacrolimus e micofenolato (p<0,001). A binucleação celular e brotamento nuclear foram associadas ao histórico de infeções virais oncogênicas e manifestação de QA (p<0,001). Portanto, a presença e a gravidade da QA em RTR estão associadas a cor da pele, fatores de risco da QA, uso de imunossupressores e histórico de infecções virais. A presença de binucleação nuclear e brotamento nuclear foram associadas à presença QA, principalmente indivíduos do sexo masculino, em uso de Tacrolimus e Micofenolato, com histórico de infecções de vírus oncogênicos e com mais de 7 anos decorridos do transplante renal.
Title in English
Analysis of carcinogenic oral biomarkers in individuals with chronic kidney disease kidney transplant recipients
Keywords in English
Carcinogenesis
Cheilitis
Kidney Transplantation
Labial neoplasms
Tumor biomarkers
Abstract in English
Kidney transplant recipients (KTR) have a risk of manifestation of lower lip squamous cell carcinoma (SCC) from 4 to 46.6 times higher than the normal population. Actinic cheilitis (AC) is a potentially malignant lesion that precedes the manifestation of lip SCC and can be identified through clinical examination. Similarly, the ways to monitor carcinogenesis in KTR is through the analysis of nuclear anomalies of the cells, in order to be able to prevent and identify early the SCC of the lower lip in KTR. Therefore, the aim of this study was to analyze the manifestation of AC and its association with the presence of nuclear anomalies in KTR, to identify biomarkers in the mouth that are associated with lower lip SCC. This study was a clinical-histopathological, observational, cross-sectional study, with a convenience sample through the clinical evaluation of AC, and histopathological identification of nuclear anomalies in the lower lip region of KTR. Clinical evaluation was performed by a single calibrated examiner, and the evaluation of nuclear anomalies was performed by two calibrated and blinded examiners. KTR information such as age, gender, skin color, dialysis time before transplantation, transplant time, immunosuppressants, risk factors such as alcohol consumption, smoking, sun exposure and history of viral infections were recorded. Clinical evaluation was performed through clinical examination and photographic analysis of the lower lip. For histopathological evaluation, lower lip cells were collected through tissue scraping and packaging in booing with methanol and colored by Feulgen reaction. Nuclear anomalies were classified as micronucleus, nuclear budding, nucleocytoplasmic bridge and binucleation. Fisher and Macnemar's exact test (p<0.05) was used for statistical analysis. The sample was 48 KTR, with a diagnosis of AC in 29 (60.41%). AC staging was associated with KTR leucodermas (p<0.05). The presence of AC was associated with a history of exposure to volatile chemical agents and smoking (p<0.05); history of use of tacrolimus, azathioprine and sirolimus (p<0.001). AC staging was associated with the use of Mycophenolato (p<0.05). The administration of lower doses of Sirolimus was associated with grade III and IV of QA (p<0.05). Epstein-Barr Virus and Herpes Simple Virus infections were associated with the presence of AC (p<0.05). Among nuclear anomalies, the cell binucleation was associated with KTR with more than 7 years of kidney transplantation (p=0.008). All nuclear anomalies were associated with the use of tacrolimus and mycophenolato (p<0.001). Cell binucleation and nuclear budding were associated with a history of oncogenic viral infections and manifestation of AC (p<0.001). Therefore, the presence and severity of AC in KRT were associated with skin color, risk factors of AC, use of immunosuppressants, and history of viral infections. The presence of nuclear binucleation and nuclear budding were associated with the presence of AC, mainly in male individuals using tacrolimus and mycophenolate, with history of oncogenic virus infections and with more than 7 years elapsed from the kidney transplantation.
 
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Publishing Date
2022-06-09
 
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