Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar
Malignant salivary gland tumors (MSGT) are rare, heterogeneous lesions with a variable prognosis. Mammalian cells are subject to thousands of spontaneous changes in the deoxyribonucleic acid (DNA) molecule. The apuric or apyrimidic endonuclease protein 1 (APE1) and the X-ray crossover complementa...
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Neoplasias das glândulas salivares Reparo do DNA DNA Liase (sítios apurínicos ou apirimidínicos) Proteína 1 complementadora cruzada de reparo de raio-X Fator de complementação F do xeroderma pigmentoso CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
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Neoplasias das glândulas salivares Reparo do DNA DNA Liase (sítios apurínicos ou apirimidínicos) Proteína 1 complementadora cruzada de reparo de raio-X Fator de complementação F do xeroderma pigmentoso CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA Felix, Fernanda Aragão Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
description |
Malignant salivary gland tumors (MSGT) are rare, heterogeneous lesions with a variable
prognosis. Mammalian cells are subject to thousands of spontaneous changes in the
deoxyribonucleic acid (DNA) molecule. The apuric or apyrimidic endonuclease protein 1
(APE1) and the X-ray crossover complementation protein 1 (XRCC1) are two important
components of the base excision repair pathway (BER), and the complementation factor
protein F of the xeroderma pigmentosum (XPF), the nucleotide excision repair pathway
(NER). This study analyzed the immunohistochemical expression of APE1 and XRCC1
proteins of the BER pathway, and XPF of the NER pathway, in a sample of primary tumors of
acinar cell carcinoma (ACC), polymorphic adenocarcinoma (PAC), adenoid cystic carcinoma
(AdCC) and mucoepidermoid carcinoma (MEC). A total of 62 MSGT were included and
submitted to immunohistochemistry against the selected antibodies, corresponding to 14
ACC, 15 PAC, 16 AdCC, and 17 MEC. The tissue sections were subjected to
immunohistochemistry for APE1, XRCC1 and XPF. The cells of the tumor parenchyma were
quantitatively evaluated, using photomicrographs of 5 fields (in 400x magnification), by a
single evaluator. Immunoreactive cells were those with brownish color in the nucleus and/or
nucleus/ cytoplasm, regardless of intensity. Immunomarked and negative cells were counted
in the 5 fields, establishing the percentage of positive cells in relation to the total number of
cells counted. In addition, it was established whether the nucleus or nucleus/cytoplasm ratio,
inferring whether the location was predominantly uni or bicompartmental. Statistical tests
included Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well as
the log-rank for comparison of the overall survival built through Kaplan-Meier method.
Significance was set at p<0.05. All selected MSGT scored for APE1, XRCC1 and XPF. There
was no difference between the expression of APE1 and XPF among the studied tumors. For
XRCC1, however, there was a significant difference between PAC and MEC (p=0.032).
Nuclear labeling of APE1 was statistically higher in the selected MSGT (p<0.0001). There
was a statistical relationship between APE1 and T1-T2 tumors in the AdCC (p=0.006), as
well as an increase in XPF in patients with MEC over 60 years (p=0.015) and AdCC in a
minor salivary gland (p=0.012), although reduced in patients treated with surgery associated
with adjuvant therapy in ACC and AdCC (p=0.036 and p=0.020, respectively). The low
expression of XRCC1 in the nucleus (p=0.028) or the expression of concomitant XRCC1 in
the nucleus and cytoplasm (p=0.017) were associated with a lower overall 5-year survival
rate. Finally, the Spearman correlation test demonstrated a positive correlation between APE
and XRCC1 in all MSGT analyzed, although the correlation among the three proteins (APE1,
XRCC1 and XPF) was observed only in AdCC and MEC (p<0.05). This study demonstrated
high expression of the repair proteins APE1, XRCC1 and XPF in ACC, PAC, AdCC, and
MEC, which may suggest regulatory activity related to the genotoxic control of these proteins
in MSGT. |
author2 |
Barboza, Carlos Augusto Galvão |
author_facet |
Barboza, Carlos Augusto Galvão Felix, Fernanda Aragão |
format |
masterThesis |
author |
Felix, Fernanda Aragão |
author_sort |
Felix, Fernanda Aragão |
title |
Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
title_short |
Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
title_full |
Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
title_fullStr |
Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
title_full_unstemmed |
Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar |
title_sort |
análise da imunoexpressão de proteínas de reparo do dna em tumores malignos de glândula salivar |
publisher |
Brasil |
publishDate |
2020 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/28977 |
work_keys_str_mv |
AT felixfernandaaragao analisedaimunoexpressaodeproteinasdereparododnaemtumoresmalignosdeglandulasalivar |
_version_ |
1773962096868851712 |
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ri-123456789-289772020-05-17T08:00:25Z Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar Felix, Fernanda Aragão Barboza, Carlos Augusto Galvão Moura, Jamile Marinho Bezerra de Oliveira Souza, Lélia Batista de Neoplasias das glândulas salivares Reparo do DNA DNA Liase (sítios apurínicos ou apirimidínicos) Proteína 1 complementadora cruzada de reparo de raio-X Fator de complementação F do xeroderma pigmentoso CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA Malignant salivary gland tumors (MSGT) are rare, heterogeneous lesions with a variable prognosis. Mammalian cells are subject to thousands of spontaneous changes in the deoxyribonucleic acid (DNA) molecule. The apuric or apyrimidic endonuclease protein 1 (APE1) and the X-ray crossover complementation protein 1 (XRCC1) are two important components of the base excision repair pathway (BER), and the complementation factor protein F of the xeroderma pigmentosum (XPF), the nucleotide excision repair pathway (NER). This study analyzed the immunohistochemical expression of APE1 and XRCC1 proteins of the BER pathway, and XPF of the NER pathway, in a sample of primary tumors of acinar cell carcinoma (ACC), polymorphic adenocarcinoma (PAC), adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC). A total of 62 MSGT were included and submitted to immunohistochemistry against the selected antibodies, corresponding to 14 ACC, 15 PAC, 16 AdCC, and 17 MEC. The tissue sections were subjected to immunohistochemistry for APE1, XRCC1 and XPF. The cells of the tumor parenchyma were quantitatively evaluated, using photomicrographs of 5 fields (in 400x magnification), by a single evaluator. Immunoreactive cells were those with brownish color in the nucleus and/or nucleus/ cytoplasm, regardless of intensity. Immunomarked and negative cells were counted in the 5 fields, establishing the percentage of positive cells in relation to the total number of cells counted. In addition, it was established whether the nucleus or nucleus/cytoplasm ratio, inferring whether the location was predominantly uni or bicompartmental. Statistical tests included Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well as the log-rank for comparison of the overall survival built through Kaplan-Meier method. Significance was set at p<0.05. All selected MSGT scored for APE1, XRCC1 and XPF. There was no difference between the expression of APE1 and XPF among the studied tumors. For XRCC1, however, there was a significant difference between PAC and MEC (p=0.032). Nuclear labeling of APE1 was statistically higher in the selected MSGT (p<0.0001). There was a statistical relationship between APE1 and T1-T2 tumors in the AdCC (p=0.006), as well as an increase in XPF in patients with MEC over 60 years (p=0.015) and AdCC in a minor salivary gland (p=0.012), although reduced in patients treated with surgery associated with adjuvant therapy in ACC and AdCC (p=0.036 and p=0.020, respectively). The low expression of XRCC1 in the nucleus (p=0.028) or the expression of concomitant XRCC1 in the nucleus and cytoplasm (p=0.017) were associated with a lower overall 5-year survival rate. Finally, the Spearman correlation test demonstrated a positive correlation between APE and XRCC1 in all MSGT analyzed, although the correlation among the three proteins (APE1, XRCC1 and XPF) was observed only in AdCC and MEC (p<0.05). This study demonstrated high expression of the repair proteins APE1, XRCC1 and XPF in ACC, PAC, AdCC, and MEC, which may suggest regulatory activity related to the genotoxic control of these proteins in MSGT. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq Os tumores malignos de glândula salivar (TMGS) são lesões raras, heterogêneas e de prognóstico variável. As células dos mamíferos estão sujeitas a milhares de modificações espontâneas na molécula de ácido desoxirribonucleico (DNA). A proteína endonuclease apúrica ou apirimídica 1 (APE1) e a proteína 1 de complementação cruzada de reparo de raios-x (XRCC1) são dois componentes importante da via de reparo por excisão de base (BER), e a proteína fator de complementação F do xeroderma pigmentoso (XPF), da via de reparo por excisão nucleotídeo (NER). Este estudo analisou a expressão imuno-histoquímica das proteínas APE1 e XRCC1 da via BER, e XPF da via NER, em amostra de tumores primários de carcinoma de células acinares (CCA), adenocarcinoma polimorfo (AcP), carcinoma adenoide cístico (CAC) e carcinoma mucoepidermoide (CME). Um total de 62 TMGS foram incluídos e submetidos à imuno-histoquímica contra os anticorpos selecionados, correspondendo a 14 CCA, 15 AcP, 16 CAC e 17 CME. As células do parênquima tumoral foram avaliadas quantitativamente, a partir de fotomicrografias de 5 campos (em aumento de 400x), por um único avaliador. Foram consideradas células imunorreativas aquelas com coloração acastanhada no núcleo e/ou núcleo/citoplasma, independente da intensidade. As células imunomarcadas e negativas foram contadas nos 5 campos, estabelecendo o porcentual de células positivas em relação ao número total de células contadas. Ademais, estabeleceu-se a razão núcleo ou núcleo/citoplasma, inferindo se a localização era predominantemente uni ou bicompartimental. Os testes estatísticos incluíram o exato de Fisher, Mann-Whitney, KruskalWallis, correlação de Spearman e log-rank para comparação das curvas de sobrevida global construídas pelo método Kaplan-Meier. O nível de significância foi estabelecido em 5%. Todos os TMGS selecionados marcaram para APE1, XRCC1 e XPF. Não houve diferença entre a expressão de APE1 e XPF entre os tumores estudados. Para XRCC1, contudo, observou-se diferença significativa entre AcP e CME (p=0.032). A marcação nuclear de APE1 foi estatisticamente maior nos TMGS selecionados (p<0.0001). Houve relação estatística de APE1 com tumores T1-T2 no CAC (p=0.006), bem como de aumento de XPF em pacientes com CME acima de 60 anos (p=0.015) e CAC em glândula salivar menor (p=0.012), embora tenha reduzido em pacientes tratados com cirurgia associado à terapia adjuvante no CCA e no CAC (p=0.036 e p=0.020, respectivamente). A baixa expressão de XRCC1 no núcleo (p=0.028) ou a expressão de XRCC1 concomitante no núcleo e no citoplasma (p=0.017) foram associadas com menor taxa de sobrevida global em 5 anos. Finalmente, o teste de correlação de Spearman demonstrou correlação positiva entre a APE e XRCC1 em todos os TMGS analisados, embora a correlação entre as três proteínas (APE1, XRCC1 e XPF) tenha sido observada apenas em CAC e CME (p<0.05). Este trabalho demonstrou alta expressão das proteínas de reparo APE1, XRCC1 e XPF em CCA, AcP, CAC e CME, o que pode sugerir atividade reguladora relacionada ao controle genotóxico dessas proteínas nos TMGS. 2020-05-13T23:51:10Z 2020-05-13T23:51:10Z 2020-02-18 masterThesis FELIX, Fernanda Aragão. Análise da imunoexpressão de proteínas de reparo do DNA em tumores malignos de glândula salivar. 2020. 118f. Dissertação (Mestrado em Ciências Odontológicas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2020. https://repositorio.ufrn.br/jspui/handle/123456789/28977 pt_BR Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS ODONTOLÓGICAS |