Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF

Detalhes bibliográficos
Autor(a) principal: Souza, Paulo Ornellas de
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/8735
Resumo: Squamous cell carcinoma of the penis (SSCP) represents 95% of penile cancers. It affects mostly uncircumcised patients and is often associated with lack of adequate local hygiene and phimosis. In Brazil, the incidence is 2.7% but in some areas of the country can reach 17% of diagnosed cases of cancer per year. The tumor can occur in any part of the sexual organ and the type of staging to be used is controversial. The Broders classification is more often used to classify tumors. Studies suggest the relationship between the development of penile carcinoma and HPV infection (Human Papilloma Virus). The evaluation method of inguinal lymph nodes remains controversial and it is difficult to differentiate inflammatory reaction from metastatic lymphadenopathy. Physical examination is not a reliable predictor of lymph node involvement since patients with palpable lymph nodes can not present metastases. There are few publications about the molecular mechanisms involved in the genesis and progression of the SSCP. Although several markers have been evaluated, currently the clinical application of these is limited. Most of the markers studied require invasive procedures for obtaining tumor tissue. There is a need to find through a minimally invasive technique circulating tumor markers able to differentiate SSCP patients with and without metastatic involvement. In this type ofmalignancythediscovery of biomarkers that assessthe prognosisis relevant since physical examination is not a reliable predictor oflymph node involvementand survival. The objectives of this study were: 1) to review and discuss the epidemiology, etiology, different types of surgical approach and controversies in the surgical treatment of penile cancer 2)to investigate via the platform ClinProt / MALDI / TOF presence of plasma markers able to discriminate healthy subjects from patients affected by squamous cell carcinoma of the penis (SCCP) 3) to evaluate the importance of these markers in disease progression. Between June 2010 and June 2011, plasma samples from 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment in the UrologyServicesofNational Cancer InstituteandMarioKröeffHospital were collected and analyzed by the ClinProt/MALDI/TOF platform. Our results found a cluster of 2 peptides (A=m/z 1897.22 +-9 Da and B=m/z 2021.99 +-9 Da that was able to discriminate patients from controls subjects. These peptides were further identified as C3 and C4 A/B fragments from complement system. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% of sensitivity and specificity, respectively with a very high sensitivity (100%) and specificity (97%) for SCCP patients that have died by disease. Moreover, patients with lymph node involvement present a sensitivity and specificity of 80% and 97%, respectively. The results showed that as the disease progresses more under express are the cluster comparing with healthy subjects. These results may be useful as prognostic toll.
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spelling Brown, Gilda Alveshttp://lattes.cnpq.br/9799832789400715Pereira, Denise de Abreuhttp://lattes.cnpq.br/3927778822203761Damião, Ronaldohttp://lattes.cnpq.br/2898947587537967Canedo, Nathalie Henriques Silvahttp://lattes.cnpq.br/4295929194142461Carvalho, Paulo Costahttp://lattes.cnpq.br/9300734296482577http://lattes.cnpq.br/5220304160127322Souza, Paulo Ornellas de2021-01-05T19:41:35Z2014-07-112013-08-28SOUZA, Paulo Ornellas de. Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF. 2013. 89 f. Dissertação (Mestrado em Ciências Médicas) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.http://www.bdtd.uerj.br/handle/1/8735Squamous cell carcinoma of the penis (SSCP) represents 95% of penile cancers. It affects mostly uncircumcised patients and is often associated with lack of adequate local hygiene and phimosis. In Brazil, the incidence is 2.7% but in some areas of the country can reach 17% of diagnosed cases of cancer per year. The tumor can occur in any part of the sexual organ and the type of staging to be used is controversial. The Broders classification is more often used to classify tumors. Studies suggest the relationship between the development of penile carcinoma and HPV infection (Human Papilloma Virus). The evaluation method of inguinal lymph nodes remains controversial and it is difficult to differentiate inflammatory reaction from metastatic lymphadenopathy. Physical examination is not a reliable predictor of lymph node involvement since patients with palpable lymph nodes can not present metastases. There are few publications about the molecular mechanisms involved in the genesis and progression of the SSCP. Although several markers have been evaluated, currently the clinical application of these is limited. Most of the markers studied require invasive procedures for obtaining tumor tissue. There is a need to find through a minimally invasive technique circulating tumor markers able to differentiate SSCP patients with and without metastatic involvement. In this type ofmalignancythediscovery of biomarkers that assessthe prognosisis relevant since physical examination is not a reliable predictor oflymph node involvementand survival. The objectives of this study were: 1) to review and discuss the epidemiology, etiology, different types of surgical approach and controversies in the surgical treatment of penile cancer 2)to investigate via the platform ClinProt / MALDI / TOF presence of plasma markers able to discriminate healthy subjects from patients affected by squamous cell carcinoma of the penis (SCCP) 3) to evaluate the importance of these markers in disease progression. Between June 2010 and June 2011, plasma samples from 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment in the UrologyServicesofNational Cancer InstituteandMarioKröeffHospital were collected and analyzed by the ClinProt/MALDI/TOF platform. Our results found a cluster of 2 peptides (A=m/z 1897.22 +-9 Da and B=m/z 2021.99 +-9 Da that was able to discriminate patients from controls subjects. These peptides were further identified as C3 and C4 A/B fragments from complement system. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% of sensitivity and specificity, respectively with a very high sensitivity (100%) and specificity (97%) for SCCP patients that have died by disease. Moreover, patients with lymph node involvement present a sensitivity and specificity of 80% and 97%, respectively. The results showed that as the disease progresses more under express are the cluster comparing with healthy subjects. These results may be useful as prognostic toll.O carcinoma epidermóide de pênis (CEP) representa 95% das neoplasias penianas e afeta quase sempre pacientes não circuncidados estando muitas vezes associado à falta de higiene local adequada e à fimose. No Brasil a sua incidência é de 2,7 % porém em algumas áreas do país pode chegar a 17% dos casos diagnosticados por ano. O tumor pode ocorrer em qualquer parte do órgão sexual masculino e o tipo de estadiamento empregado é controverso. A classificação de Broders é a mais utilizada. Estudos sugerem a relação entre o desenvolvimento do carcinoma de pênis com a infecção por HPV (Papiloma Vírus Humano). O método de avaliação dos linfonodos inguinais permanece controverso sendo difícil a diferenciação entre linfadenomegalia inflamatória reacional e metastática. O exame físico não é um preditor confiável do comprometimento linfonodal pois pacientes com linfonodos palpáveis podem não apresentar metástases. Há poucas publicações sobre os mecanismos moleculares envolvidos na gênese e progressão do CEP. Apesar de vários marcadores terem sido avaliados, atualmente a aplicação clínica destes é limitada. A maior parte dos marcadores estudados requer procedimentos invasivos para obtenção do tecido tumoral. Existe a necessidade de encontrar através de uma técnica pouco invasiva marcadores tumorais circulantes capazes de diferenciar portadores de CEP com e sem envolvimento metastático. Neste tipo de neoplasia, a descoberta de biomarcadores que avaliem o prognóstico é relevante, pois o exame físico não é um indicador confiável do comprometimento linfonodal e da sobrevida.Os objetivos foram 1) revisar e discutir a epidemiologia, a etiologia, os diversos tipos de abordagem cirúrgica e as controvérsias no tratamento cirúrgico do câncer de pênis 2) investigar através da plataforma ClinProt/ MALDI / TOF a presença de marcadores plasmáticos capazes de discriminar indivíduos saudáveis de pacientes afetados por carcinoma epidermóide de pênis (CEP) 3) avaliar a importância destes marcadores na evolução da doença. Foram coletados e analisados pela plataforma ClinProt / MALDI / TOF o plasma de 36 indivíduos saudáveis e 25 pacientes com CEP invasivo, submetidos a tratamento cirúrgico entre junho de 2010 e junho de 2011, nos serviços de urologia do Instituto Nacional de Câncer e do Hospital Mário Kröeff (Rio de Janeiro). Nossos resultados apontaram para um conjunto de dois peptídeos (A = m / z 1897,22 + -9 Da e B = m / z 2021,99 + -9 Da) que foram capazes de diferenciar pacientes com CEP de indivíduos controles. Esses peptídeos foram posteriormente identificados como fragmentos C3 e C4 A/B do sistema complemento. A validação cruzada, utilizando toda casuística apresentou 62,5% e 86,76% de sensibilidade e de especificidade, respectivamente, com uma alta sensibilidade (100%) e especificidade (97%) nos pacientes que morreram pela doença. Além disso, os pacientes com envolvimento ganglionar obtiveram uma sensibilidade e uma especificidade de 80 % e 97%, respectivamente. Ficou demonstrado que à medida que a doença progride mais subexpressos está o conjunto de peptídeos quando comparados com indivíduos saudáveis. Estes resultados podem ser úteis como ferramentas para a avaliação do prognóstico destes pacientes.Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T19:41:35Z No. of bitstreams: 1 DISSERTACAO_FINAL_Paulo Ornellas de Souza.pdf: 5700098 bytes, checksum: 6b717b2aa67ee5400fb93b10c679c825 (MD5)Made available in DSpace on 2021-01-05T19:41:35Z (GMT). No. of bitstreams: 1 DISSERTACAO_FINAL_Paulo Ornellas de Souza.pdf: 5700098 bytes, checksum: 6b717b2aa67ee5400fb93b10c679c825 (MD5) Previous issue date: 2013-08-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em Ciências MédicasUERJBRCentro Biomédico::Faculdade de Ciências MédicasPenile câncerLimphadenectomySubexpression of fragments C3 and C4A / B of the complement systemProteomicsPlatform ClinProt / MALDI / TOFCâncer de pênisLinfadenectomiaSubexpressão dos fragmentos C3 e C4A/B do sistema complementoProteômicaPlataforma ClinProt/MALDI/TOFPênis CâncerNeoplasias Penianas CirurgiaExcisão de LinfonodoEspectrometria de Massas InstrumentaçãoCNPQ::CIENCIAS DA SAUDE::MEDICINACarcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOFInvasive squamous cell carcinoma of the penis: subexpression of the fragments C3 and C4A/B of the complement system detected in plasma by proteomic platform ClinProt / MALDI / TOFinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDISSERTACAO_FINAL_Paulo Ornellas de Souza.pdfapplication/pdf5700098http://www.bdtd.uerj.br/bitstream/1/8735/1/DISSERTACAO_FINAL_Paulo+Ornellas+de+Souza.pdf6b717b2aa67ee5400fb93b10c679c825MD511/87352024-02-26 16:00:01.991oai:www.bdtd.uerj.br:1/8735Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T19:00:01Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
dc.title.alternative.eng.fl_str_mv Invasive squamous cell carcinoma of the penis: subexpression of the fragments C3 and C4A/B of the complement system detected in plasma by proteomic platform ClinProt / MALDI / TOF
title Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
spellingShingle Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
Souza, Paulo Ornellas de
Penile câncer
Limphadenectomy
Subexpression of fragments C3 and C4A / B of the complement system
Proteomics
Platform ClinProt / MALDI / TOF
Câncer de pênis
Linfadenectomia
Subexpressão dos fragmentos C3 e C4A/B do sistema complemento
Proteômica
Plataforma ClinProt/MALDI/TOF
Pênis Câncer
Neoplasias Penianas Cirurgia
Excisão de Linfonodo
Espectrometria de Massas Instrumentação
CNPQ::CIENCIAS DA SAUDE::MEDICINA
title_short Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
title_full Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
title_fullStr Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
title_full_unstemmed Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
title_sort Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF
author Souza, Paulo Ornellas de
author_facet Souza, Paulo Ornellas de
author_role author
dc.contributor.advisor1.fl_str_mv Brown, Gilda Alves
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9799832789400715
dc.contributor.advisor-co1.fl_str_mv Pereira, Denise de Abreu
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/3927778822203761
dc.contributor.referee1.fl_str_mv Damião, Ronaldo
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/2898947587537967
dc.contributor.referee2.fl_str_mv Canedo, Nathalie Henriques Silva
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/4295929194142461
dc.contributor.referee3.fl_str_mv Carvalho, Paulo Costa
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/9300734296482577
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5220304160127322
dc.contributor.author.fl_str_mv Souza, Paulo Ornellas de
contributor_str_mv Brown, Gilda Alves
Pereira, Denise de Abreu
Damião, Ronaldo
Canedo, Nathalie Henriques Silva
Carvalho, Paulo Costa
dc.subject.eng.fl_str_mv Penile câncer
Limphadenectomy
Subexpression of fragments C3 and C4A / B of the complement system
Proteomics
Platform ClinProt / MALDI / TOF
topic Penile câncer
Limphadenectomy
Subexpression of fragments C3 and C4A / B of the complement system
Proteomics
Platform ClinProt / MALDI / TOF
Câncer de pênis
Linfadenectomia
Subexpressão dos fragmentos C3 e C4A/B do sistema complemento
Proteômica
Plataforma ClinProt/MALDI/TOF
Pênis Câncer
Neoplasias Penianas Cirurgia
Excisão de Linfonodo
Espectrometria de Massas Instrumentação
CNPQ::CIENCIAS DA SAUDE::MEDICINA
dc.subject.por.fl_str_mv Câncer de pênis
Linfadenectomia
Subexpressão dos fragmentos C3 e C4A/B do sistema complemento
Proteômica
Plataforma ClinProt/MALDI/TOF
Pênis Câncer
Neoplasias Penianas Cirurgia
Excisão de Linfonodo
Espectrometria de Massas Instrumentação
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
description Squamous cell carcinoma of the penis (SSCP) represents 95% of penile cancers. It affects mostly uncircumcised patients and is often associated with lack of adequate local hygiene and phimosis. In Brazil, the incidence is 2.7% but in some areas of the country can reach 17% of diagnosed cases of cancer per year. The tumor can occur in any part of the sexual organ and the type of staging to be used is controversial. The Broders classification is more often used to classify tumors. Studies suggest the relationship between the development of penile carcinoma and HPV infection (Human Papilloma Virus). The evaluation method of inguinal lymph nodes remains controversial and it is difficult to differentiate inflammatory reaction from metastatic lymphadenopathy. Physical examination is not a reliable predictor of lymph node involvement since patients with palpable lymph nodes can not present metastases. There are few publications about the molecular mechanisms involved in the genesis and progression of the SSCP. Although several markers have been evaluated, currently the clinical application of these is limited. Most of the markers studied require invasive procedures for obtaining tumor tissue. There is a need to find through a minimally invasive technique circulating tumor markers able to differentiate SSCP patients with and without metastatic involvement. In this type ofmalignancythediscovery of biomarkers that assessthe prognosisis relevant since physical examination is not a reliable predictor oflymph node involvementand survival. The objectives of this study were: 1) to review and discuss the epidemiology, etiology, different types of surgical approach and controversies in the surgical treatment of penile cancer 2)to investigate via the platform ClinProt / MALDI / TOF presence of plasma markers able to discriminate healthy subjects from patients affected by squamous cell carcinoma of the penis (SCCP) 3) to evaluate the importance of these markers in disease progression. Between June 2010 and June 2011, plasma samples from 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment in the UrologyServicesofNational Cancer InstituteandMarioKröeffHospital were collected and analyzed by the ClinProt/MALDI/TOF platform. Our results found a cluster of 2 peptides (A=m/z 1897.22 +-9 Da and B=m/z 2021.99 +-9 Da that was able to discriminate patients from controls subjects. These peptides were further identified as C3 and C4 A/B fragments from complement system. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% of sensitivity and specificity, respectively with a very high sensitivity (100%) and specificity (97%) for SCCP patients that have died by disease. Moreover, patients with lymph node involvement present a sensitivity and specificity of 80% and 97%, respectively. The results showed that as the disease progresses more under express are the cluster comparing with healthy subjects. These results may be useful as prognostic toll.
publishDate 2013
dc.date.issued.fl_str_mv 2013-08-28
dc.date.available.fl_str_mv 2014-07-11
dc.date.accessioned.fl_str_mv 2021-01-05T19:41:35Z
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dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv SOUZA, Paulo Ornellas de. Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF. 2013. 89 f. Dissertação (Mestrado em Ciências Médicas) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.
dc.identifier.uri.fl_str_mv http://www.bdtd.uerj.br/handle/1/8735
identifier_str_mv SOUZA, Paulo Ornellas de. Carcinoma epidermóide invasivo de pênis: subexpressão dos fragmentos C3 e C4A/B do sistema complemento detectado no plasma pela plataforma proteômica ClinProt/MALDI/TOF. 2013. 89 f. Dissertação (Mestrado em Ciências Médicas) - Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2013.
url http://www.bdtd.uerj.br/handle/1/8735
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