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Doctoral Thesis
DOI
10.11606/T.23.2008.tde-08042009-113006
Document
Author
Full name
Helder Antonio Rebêlo Pontes
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Pinto Júnior, Décio dos Santos (President)
Kataoka, Maria Sueli da Silva
Mesquita, Ricardo Alves de
Sousa, Suzana Cantanhede Orsini Machado de
Wisniewski, Ana Carolina Thomé Capuano
Title in Portuguese
Avaliação imunoistoquímica das proteínas metalotioneína, pAKT e NF-kB como marcadores de prognóstico de carcinomas epidermóides de boca
Keywords in Portuguese
Akt
Carcinoma epidermóide
Metalotioneína
NF-kB
Sobrevida.
Abstract in Portuguese
O carcinoma epidermóide é a neoplasia maligna que ocorre com maior freqüência na boca. Os pacientes portadores desta neoplasia ainda apresentam um pobre prognóstico com índices de sobrevida, em cinco anos, variando de 20 a 40% em vários estudos. Um grande número de trabalhos tem sido direcionado para identificar marcadores que auxiliem no direcionamento do tratamento e melhorem o prognóstico. A metalotioneína (MT) é uma proteína de baixo peso molecular, com alto conteúdo de cisteína e que está associada à resistência neoplásica a várias modalidades de tratamento, e que por isso tem sido estudada como fator prognóstico em uma variedade de neoplasias malignas humanas. O Fator Nuclear B desempenha um importante papel na ativação de genes que estão relacionados à imunidade, inflamação, sobrevida, apoptose, proteção celular à radiação e à quimioterapia. A proteína serina/treonina quinase Akt é um alvo downstream da quinase 3-fosfaditilinositol, desempenhando um importante papel na proliferação e no bloqueio da apoptose de células cancerígenas. Neste estudo, nós examinamos a expressão das proteínas MT, NF-kB e pAKT em 51 casos de carcinomas epidermóides de boca, através de imunoistoquímica, com a finalidade de investigar suas influências prognosticas, assim como estudar as correlações entre alguns fatores clínicos com a sobrevida. Os resultados mostraram uma associação estatisticamente significante entre a expressão pAkt e NF-kB e entre MT e NF-kB. Ao lado disso, nossos resultados mostraram que a expressão de pAkt está associada a um pior prognóstico. Nossos resultados, portanto, sugerem que a proteína pAkt pode ter implicações terapêuticas em carcinomas epidermóides de boca.
Title in English
Immunohistochemical evaluation of Metallothionein, pAkt and NF-kB proteins as prognostic factors of Oral Squamous Cell Carcinoma
Keywords in English
Metallothionein
NF-kB
pAkt
Survival.
Abstract in English
Oral squamous cell carcinoma (OSCC) is the most frequent malignant tumor of the oral cavity. In spite of improved therapeutic procedures, patients with OSCC in advanced stage generally present a poor prognosis, with an overall 5-year survival rate that ranges from 20% to 40%. An extensive effort has started to identify features of the oral tumors that predict treatment response and prognosis. The metallothionein (MT), a low-molecular weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. The nuclear factor B (NF-B) plays an important role in the activation of the genes that code for immunity, survival, inflammation, apoptosis and in the cell protection for radiation and chemotherapy. The serine/threonine protein kinase Akt is a downstream target of phosphatidylinositol-3-kinase and it plays a key regulator of cancerous cell growth. Therefore, we have examined the MT, NF-kB and pAkt expression in 51 samples of oral squamous cell carcinoma by immunohistochemistry in order to investigate their prognostic influence on oral cancer, as well as studying the correlations between clinical factors and patient survival. The results showed a significant association between pAkt and NF-kB and between MT and NF-kB expression in tumor tissue. Besides pAkt over-expression was found in OSCC clinical samples and its expression was significantly associated with a poor overall patient survival. In conclusion, our findings suggested that pAkt expression may have therapeutic implications in squamous cell carcinoma.
 
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Publishing Date
2009-06-08
 
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