Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Silva, Constanza Thaise Xavier lattes
Orientador(a): Guillo, Lidia Andreu lattes
Banca de defesa: Guillo, Lidia Andreu lattes, Saddi, Vera Aparecida lattes, Costa, Cesar Augusto Sam Tiago Vila Nova, Carneiro, Lilian Carla, Arruda, Jalsi Tacon
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
dARK ID: ark:/38995/0013000001snv
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Programa de Pós-graduação em Ciências da Saúde (FM)
Departamento: Faculdade de Medicina - FM (RG)
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/6620
Resumo: Cutaneous melanoma is a type of skin cancer that originates in melanocytes, predominantly affecting young and middle-aged adults. Several evidence suggests that cancer stem cells exist for melanoma. The POU5F1 / OCT4, NANOG genes have been studied as cancer stem markers. OCT4 and NANOG are involved in the maintenance of pluripotency and self-renewal of undifferentiated embryonic stem cells. This study aims to evaluate the epidemiological, clinical-pathological and expression of the OCT4 and NANOG proteins in cutaneous melanoma samples. We selected 102 cases for the epidemiological, clinical and pathological study, diagnosed between the years 2004 to 2008. For survival study, patients with a followup of up to 60 months were selected, with a recorded death. Of the 102 cases evaluated, 62.7% were female and 37.3% male; With mean age of 57.2 years and 63.1 years respectively (p= 0.0026). The most prevalent age at diagnosis of melanoma was between 51 and 70 years (44.1% p= 0.023). In this study, there was a predominance of lesions located in the trunk (32.3%). Histopathological examination of the type of tumor growth showed a predominance of the superficial extensive type in 52.9% of the cases. According to the Breslow index, lesions with ≤1.0 mm predominated in 39.2% of the individuals, followed by lesions> 4.0 mm in 23.5% of the cases. According to the Clark level 29.4% of the cases were classified in level IV; Followed by 25.5% cases with level V; Clark II in 23.5%; Clark III in 20.6%; And Clark I in only 1 case (1.0%). There were metastases in 47% of the cases and the main localization sites were: lymph nodes, brain, skin and lung. Regarding the clinical evolution of the patients, there were 26 cases of deaths due to melanoma (25.5%). The survival curve calculated at the 60-month follow-up was 73.0%. Univariate analysis revealed significant associations between nuclear overexpression of OCT4 and the following variables: Breslow index with thickness > 2.1 mm (p = 0.021, OR: 2.64, 95% CI: 1.15-6.05 ); Levels of Clark, IV and V (p = 0.001, OR: 4.11, 95% CI: 1.79-9.46); ulceration present (p≤0.0001; OR: 459.0; 95% CI: 51.67-4077.27); Presence of metastases (p <0.0001, OR: 40.25, 95% CI: 12.90- 125.62), and death from cutaneous melanoma (p <0.0001). The significant associations between cytoplasmic hyperexpression of OCT4 and the following variables were: present ulceration (p = 0.015, OR: 2.73, 95% CI: 1.21-6.16); Presence of metastases (p = 0.004, OR: 3.34, 95% CI: 1.47 - 7.62) and death from cutaneous melanoma (p = 0.039, OR 2.67, 95% CI 1.05 - 6,77). And the significant associations between the cytoplasmic hyperexpression of NANOG and the following variables were: present ulceration (p≤ 0.0001); Presence of metastases (p ≤ 0.0001) and death due to cutaneous melanoma (p = 0.030). Our study demonstrated a strong association of the OCT4
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spelling Guillo, Lidia Andreuhttp://lattes.cnpq.br/3401436781775091Saddi, Vera Aparecidahttp://lattes.cnpq.br/7496804650895441Guillo, Lidia Andreuhttp://lattes.cnpq.br/3401436781775091Saddi, Vera Aparecidahttp://lattes.cnpq.br/7496804650895441Costa, Cesar Augusto Sam Tiago Vila NovaCarneiro, Lilian CarlaArruda, Jalsi Taconhttp://lattes.cnpq.br/7751669419978087Silva, Constanza Thaise Xavier2016-12-26T12:28:18Z2016-12-13SILVA, C. T. X. Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo. 2016. 127 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2016.http://repositorio.bc.ufg.br/tede/handle/tede/6620ark:/38995/0013000001snvCutaneous melanoma is a type of skin cancer that originates in melanocytes, predominantly affecting young and middle-aged adults. Several evidence suggests that cancer stem cells exist for melanoma. The POU5F1 / OCT4, NANOG genes have been studied as cancer stem markers. OCT4 and NANOG are involved in the maintenance of pluripotency and self-renewal of undifferentiated embryonic stem cells. This study aims to evaluate the epidemiological, clinical-pathological and expression of the OCT4 and NANOG proteins in cutaneous melanoma samples. We selected 102 cases for the epidemiological, clinical and pathological study, diagnosed between the years 2004 to 2008. For survival study, patients with a followup of up to 60 months were selected, with a recorded death. Of the 102 cases evaluated, 62.7% were female and 37.3% male; With mean age of 57.2 years and 63.1 years respectively (p= 0.0026). The most prevalent age at diagnosis of melanoma was between 51 and 70 years (44.1% p= 0.023). In this study, there was a predominance of lesions located in the trunk (32.3%). Histopathological examination of the type of tumor growth showed a predominance of the superficial extensive type in 52.9% of the cases. According to the Breslow index, lesions with ≤1.0 mm predominated in 39.2% of the individuals, followed by lesions> 4.0 mm in 23.5% of the cases. According to the Clark level 29.4% of the cases were classified in level IV; Followed by 25.5% cases with level V; Clark II in 23.5%; Clark III in 20.6%; And Clark I in only 1 case (1.0%). There were metastases in 47% of the cases and the main localization sites were: lymph nodes, brain, skin and lung. Regarding the clinical evolution of the patients, there were 26 cases of deaths due to melanoma (25.5%). The survival curve calculated at the 60-month follow-up was 73.0%. Univariate analysis revealed significant associations between nuclear overexpression of OCT4 and the following variables: Breslow index with thickness > 2.1 mm (p = 0.021, OR: 2.64, 95% CI: 1.15-6.05 ); Levels of Clark, IV and V (p = 0.001, OR: 4.11, 95% CI: 1.79-9.46); ulceration present (p≤0.0001; OR: 459.0; 95% CI: 51.67-4077.27); Presence of metastases (p <0.0001, OR: 40.25, 95% CI: 12.90- 125.62), and death from cutaneous melanoma (p <0.0001). The significant associations between cytoplasmic hyperexpression of OCT4 and the following variables were: present ulceration (p = 0.015, OR: 2.73, 95% CI: 1.21-6.16); Presence of metastases (p = 0.004, OR: 3.34, 95% CI: 1.47 - 7.62) and death from cutaneous melanoma (p = 0.039, OR 2.67, 95% CI 1.05 - 6,77). And the significant associations between the cytoplasmic hyperexpression of NANOG and the following variables were: present ulceration (p≤ 0.0001); Presence of metastases (p ≤ 0.0001) and death due to cutaneous melanoma (p = 0.030). Our study demonstrated a strong association of the OCT4O melanoma cutâneo é um tipo de câncer de pele que tem origem nos melanócitos, afetando predominantemente adultos jovens e de meia-idade. Diversas evidências sugerem a existência células-tronco tumorais para o melanoma. Os genes POU5F1/OCT4, NANOG vem sendo estudados como marcadores células-tronco tumorais. O OCT4 e o NANOG estão envolvidos na manutenção da pluripotência e autorrenovação das células-tronco embrionárias indiferenciadas. Este estudo tem por objetivo avaliar os fatores epidemiológicos, clínico-patológicos e expressão da proteína OCT4 e NANOG em amostras de melanoma cutâneo. Foram selecionados 102 casos para o estudo epidemiológico, clínico e patológico, diagnosticados entre os anos de 2004 a 2008. Para estudo de sobrevida foram selecionadas pacientes com seguimento de até 60 meses, com óbito registrado. Dos 102 casos avaliados foram observados 62,7% do gênero feminino e 37,3% masculino; com média de idade de 57,2 anos e 63,1 respectivamente (p= 0,0026). A idade de maior prevalência ao diagnóstico do melanoma foi entre 51 a 70 anos (44,1% p= 0,023). Nesse estudo, houve predomínio das lesões localizadas no tronco (32,3%). Ao exame histopatológico quanto ao tipo de crescimento do tumor, houve predomínio do tipo extensivo superficial em 52,9% dos casos. Segundo o índice de Breslow predominaram as lesões com ≤1,0mm em 39,2% dos indivíduos, seguidas pelas lesões >4,0mm em 23,5% dos casos. De acordo com o nível de Clark 29,4% dos casos foram classificados no nível IV; seguidas por 25,5% casos com nível V; Clark II em 23,5%; Clark III em 20,6%; e Clark I em apenas 1 caso (1,0%). Houve metástases em 47% dos casos e os principais sítios de localização foram: linfonodos, cérebro, pele e pulmão. Em relação à evolução clínica dos pacientes ocorreram 26 casos de óbitos por melanoma (25,5%). A curva de sobrevida calculada no seguimento de 60 meses foi de 73,0%. A análise univariada revelou associações significativas entre a hiperexpressão nuclear de OCT4 e as seguintes variáveis: índice de Breslow com espessura de > 2,1 mm (p= 0,021; OR: 2,64; IC 95%: 1,15 - 6,05); níveis de Clark, IV e V (p= 0,001; OR: 4,11; IC 95%: 1,79 - 9,46); ulceração presente (p≤ 0,0001; OR: 459,0; IC 95%: 51,67 - 4077,27); presença de metástases (p≤ 0,0001; OR: 40,25; IC 95%: 12,90 - 125,62) e óbito por melanoma cutâneo (p≤ 0,0001). As associações significativas entre a hiperexpressão citoplasmática de OCT4 e as seguintes variáveis foram: ulceração presente (p= 0,015; OR: 2,73; IC 95%: 1,21 - 6,16); presença de metástases (p= 0,004; OR: 3,34; IC 95%: 1,47 - 7,62) e óbito por melanoma cutâneo (p= 0,039; OR: 2,67; IC 95%: 1,05 - 6,77). E as associações significativas entre a hiperexpressão citoplasmática de NANOG e as seguintes variáveis foram: ulceração presente (p≤ 0,0001); presença de metástases (p≤ 0,0001) e óbito por melanoma cutâneo (p= 0,030). Nosso estudo demostraram uma forte associação dos genes OCT4 e NANOG como os piores fatores prognósticos do melanoma cutâneo.application/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências da Saúde (FM)UFGBrasilFaculdade de Medicina - FM (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessMelanomaCélulas-tronco tumoraisImunohistoquímicaNANOG e OCT4MelanomaCancer stem cellsImmunohistochemistryNANOG and OCT4MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICAAnálise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneoAnalysis of epidemiological, clinical and pathological factors and expression of OCT4 and NANOG proteins in cutaneous melanoma samplesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-100686431261774531060060060015457724759504863387337577453819502453reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
dc.title.alternative.eng.fl_str_mv Analysis of epidemiological, clinical and pathological factors and expression of OCT4 and NANOG proteins in cutaneous melanoma samples
title Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
spellingShingle Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
Silva, Constanza Thaise Xavier
Melanoma
Células-tronco tumorais
Imunohistoquímica
NANOG e OCT4
Melanoma
Cancer stem cells
Immunohistochemistry
NANOG and OCT4
MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
title_short Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
title_full Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
title_fullStr Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
title_full_unstemmed Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
title_sort Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo
author Silva, Constanza Thaise Xavier
author_facet Silva, Constanza Thaise Xavier
author_role author
dc.contributor.advisor1.fl_str_mv Guillo, Lidia Andreu
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3401436781775091
dc.contributor.advisor-co1.fl_str_mv Saddi, Vera Aparecida
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/7496804650895441
dc.contributor.referee1.fl_str_mv Guillo, Lidia Andreu
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/3401436781775091
dc.contributor.referee2.fl_str_mv Saddi, Vera Aparecida
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7496804650895441
dc.contributor.referee3.fl_str_mv Costa, Cesar Augusto Sam Tiago Vila Nova
dc.contributor.referee4.fl_str_mv Carneiro, Lilian Carla
dc.contributor.referee5.fl_str_mv Arruda, Jalsi Tacon
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/7751669419978087
dc.contributor.author.fl_str_mv Silva, Constanza Thaise Xavier
contributor_str_mv Guillo, Lidia Andreu
Saddi, Vera Aparecida
Guillo, Lidia Andreu
Saddi, Vera Aparecida
Costa, Cesar Augusto Sam Tiago Vila Nova
Carneiro, Lilian Carla
Arruda, Jalsi Tacon
dc.subject.por.fl_str_mv Melanoma
Células-tronco tumorais
Imunohistoquímica
NANOG e OCT4
topic Melanoma
Células-tronco tumorais
Imunohistoquímica
NANOG e OCT4
Melanoma
Cancer stem cells
Immunohistochemistry
NANOG and OCT4
MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.subject.eng.fl_str_mv Melanoma
Cancer stem cells
Immunohistochemistry
NANOG and OCT4
dc.subject.cnpq.fl_str_mv MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
description Cutaneous melanoma is a type of skin cancer that originates in melanocytes, predominantly affecting young and middle-aged adults. Several evidence suggests that cancer stem cells exist for melanoma. The POU5F1 / OCT4, NANOG genes have been studied as cancer stem markers. OCT4 and NANOG are involved in the maintenance of pluripotency and self-renewal of undifferentiated embryonic stem cells. This study aims to evaluate the epidemiological, clinical-pathological and expression of the OCT4 and NANOG proteins in cutaneous melanoma samples. We selected 102 cases for the epidemiological, clinical and pathological study, diagnosed between the years 2004 to 2008. For survival study, patients with a followup of up to 60 months were selected, with a recorded death. Of the 102 cases evaluated, 62.7% were female and 37.3% male; With mean age of 57.2 years and 63.1 years respectively (p= 0.0026). The most prevalent age at diagnosis of melanoma was between 51 and 70 years (44.1% p= 0.023). In this study, there was a predominance of lesions located in the trunk (32.3%). Histopathological examination of the type of tumor growth showed a predominance of the superficial extensive type in 52.9% of the cases. According to the Breslow index, lesions with ≤1.0 mm predominated in 39.2% of the individuals, followed by lesions> 4.0 mm in 23.5% of the cases. According to the Clark level 29.4% of the cases were classified in level IV; Followed by 25.5% cases with level V; Clark II in 23.5%; Clark III in 20.6%; And Clark I in only 1 case (1.0%). There were metastases in 47% of the cases and the main localization sites were: lymph nodes, brain, skin and lung. Regarding the clinical evolution of the patients, there were 26 cases of deaths due to melanoma (25.5%). The survival curve calculated at the 60-month follow-up was 73.0%. Univariate analysis revealed significant associations between nuclear overexpression of OCT4 and the following variables: Breslow index with thickness > 2.1 mm (p = 0.021, OR: 2.64, 95% CI: 1.15-6.05 ); Levels of Clark, IV and V (p = 0.001, OR: 4.11, 95% CI: 1.79-9.46); ulceration present (p≤0.0001; OR: 459.0; 95% CI: 51.67-4077.27); Presence of metastases (p <0.0001, OR: 40.25, 95% CI: 12.90- 125.62), and death from cutaneous melanoma (p <0.0001). The significant associations between cytoplasmic hyperexpression of OCT4 and the following variables were: present ulceration (p = 0.015, OR: 2.73, 95% CI: 1.21-6.16); Presence of metastases (p = 0.004, OR: 3.34, 95% CI: 1.47 - 7.62) and death from cutaneous melanoma (p = 0.039, OR 2.67, 95% CI 1.05 - 6,77). And the significant associations between the cytoplasmic hyperexpression of NANOG and the following variables were: present ulceration (p≤ 0.0001); Presence of metastases (p ≤ 0.0001) and death due to cutaneous melanoma (p = 0.030). Our study demonstrated a strong association of the OCT4
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-12-26T12:28:18Z
dc.date.issued.fl_str_mv 2016-12-13
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
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dc.identifier.citation.fl_str_mv SILVA, C. T. X. Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo. 2016. 127 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2016.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/6620
dc.identifier.dark.fl_str_mv ark:/38995/0013000001snv
identifier_str_mv SILVA, C. T. X. Análise dos fatores epidemiológicos, clínico-patológicos e expressão das proteínas OCT4 e NANOG em amostras de melanoma cutâneo. 2016. 127 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2016.
ark:/38995/0013000001snv
url http://repositorio.bc.ufg.br/tede/handle/tede/6620
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv -1006864312617745310
dc.relation.confidence.fl_str_mv 600
600
600
dc.relation.department.fl_str_mv 1545772475950486338
dc.relation.cnpq.fl_str_mv 7337577453819502453
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Ciências da Saúde (FM)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Faculdade de Medicina - FM (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
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instname:Universidade Federal de Goiás (UFG)
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instname_str Universidade Federal de Goiás (UFG)
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institution UFG
reponame_str Repositório Institucional da UFG
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