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Previous issue date: 2015-08-31 / Excluindo-se os tumores de pele n?o-melanoma, o c?ncer colorretal ? o segundo mais comum no sudeste do Brasil; o terceiro na regi?o sul e na regi?o Centro-Oeste. J? no norte do Brasil, ? o quarto e, na regi?o Nordeste, o quinto. Avaliar vari?veis clinico-patol?gicos do c?ncer colorretal ? de fundamental import?ncia para se conhecer poss?veis desfechos na sobrevida dos pacientes portadores e pontuar caracter?sticas na progress?o tumoral como o perfil da invas?o tumoral e angiog?nese. O objetivo desse trabalho ? estudar as caracter?sticas cl?nico-patol?gicas dos pacientes portadores do c?ncer colorretal (CCR) na Liga Norte Riograndense contra o c?ncer em Natal-RN/BR, analisando as vari?veis cl?nicas e patol?gicas como par?metros de progn?stico e determinando o n?vel de express?o de prote?nas, tais sejam: E-caderina (E-cad), Beta-catenina (?-cat), Galectina-3 (Gal-3), Metaloproteinases de matriz (MMP) 2 e 9 e o Fator alfa de crescimento v?sculo-endotelial (VEGF-?) nos tecidos tumorais. Foi realizado um estudo retrospectivo dos casos de c?ncer colorretal da Liga Norte-Riograndense contra o C?ncer no per?odo de 1995 a 2005 em Natal-RN / Brasil. As vari?veis cl?nico-patol?gicas, tais como: idade, sexo, etnia, h?bitos de vida, hist?ria familiar, local do tumor prim?rio, grau de diferencia??o, estadiamento TNM, Dukes? modificado, tratamento e sobrevida foram analisadas. Os dados cl?nico-patol?gicos foram coletados dos prontu?rios m?dicos atrav?s de um formul?rio espec?fico e os dados foram armazenados em uma planilha do Excel. Um total de 534 pacientes foi selecionado do arquivo do setor da patologia dessa institui??o, mas 176 pacientes foram exclu?dos. 358 pacientes foram inclu?dos para an?lise epidemiol?gica e suas correla??es cl?nico-patol?gicas foram realizadas. 180 pacientes foram selecionados para estudos histol?gicos e imunohistoqu?micos. Prote?nas participantes da progress?o tumoral E-caderina, Beta-catenina, Galectina-3, Metaloproteinases 2 e 9 e o Fator alfa de crescimento endotelial vascular foram analisadas. Os blocos de parafina dessas amostras foram tratados pela t?cnica de Tissue Microarray e suas l?minas submetidas a imunohistoqu?mica para avaliar a intensidade de marca??o dessas prote?nas nos tecidos tumorais. Os resultados dessa an?lise foram correlacionados ?s vari?veis cl?nico-patol?gicas dos pacientes. An?lise estat?stica pelo Teste de qui-quadro de Pearson e an?lise de sobrevida pela Curva de Kaplan-Meier foram utilizados. Valores de p<0,05 foram considerados estatisticamente significativos. A m?dia de idade da nossa amostra foi de 58,8 anos e 51,7% foram do sexo feminino. O consumo de ?lcool aumentou em 1,71 vezes o risco de morte pelo CCR (p=0,034). J? o tabaco aumentou 2,7 vezes a chance de desenvolver tumores de alto est?gio TNM (p=0,001). Os pacientes com hist?rico familiar de c?ncer teve 3,833 vezes a chance de desenvolver o CCR (p=0,002). A express?o da MMP-2 mostrou uma associa??o significativa com os tumores de alto est?gio TNM (p<0,046) e mortalidade (p=0,041). A express?o do ? VEGF teve correla??o estatisticamente significante com o alto est?gio TNM (p<0,009), grau de indiferencia??o celular (p<0,025) e mortalidade (p<0,035). As express?es da E-caderina e Beta-catetina mostraram associa??o do tumor com alto est?gio TNM (p=0,0001) e Dukes? modificado (p=0,05), les?o em reto (p=0,03 e p=0,007, respectivamente), tabaco (p=0,05) e indiferencia??o (p=0,001). A express?o das Gal-3 apresentou relev?ncia estat?stica com pacientes de alto est?gio TNM (p=0,01), fumantes (p=0,01), etilista (p=0,03), indiferencia??o (p=0,0001) e mortalidade (p=0,0001). Frente aos resultados, pode-se perceber que o estilo de vida e hist?rico familiar teve correla??o no progn?stico do CCR, assim como a express?o de MMP-2, MMP-9, VEGF alfa, E-caderina, Beta-catenina e Galectina-3 foram importantes marcadores de progn?stico na progress?o tumoral no c?ncer colorretal. / Except the non-melanoma skin tumors, colorectal cancer is the second most
common in the Southeastern Region of Brazil, the third most common in the Southern
and Central Regions. It is also the forth most common in the Northern Region
and it is the fifth one in the Northeastern. To assess pathological and clinical variables
of colorectal Cancer is crucial to know the possible conclusions for the survival
of patients and point out the characteristics in the progress of tumor, such as the
profile of tumor invasion and its angiogenesis. This work focuses on analyzing clinically
and pathologically some settings in colorectal cancer patients (CRC) in the city
of Natal and its countryside through those variables as parameters of prognosis and
determine the level of protein expression, for instance: E-cadherin (E-cad), beta-
-catenin (?-cat), galectin-3 (gal-3), matrix metalloproteinases (MMP) 2 and 9 and
vascular-endothelial growth factor alpha (? VEGF) in the tumor tissues. A retrospective
study was done in colorectal cancer cases in the regions of Rio Grande do
Norte state from 1995 to 2005, specifically in Natal city/RN/Brazil. The pathological
and clinical variables, such as: age, gender, ethnicity, lifestyle, family history, the
location of the primary tumor, level of differentiation, TDM staging, modified Dukes?,
treatment and survival were analyzed. The pathological and clinical data were collected
from medical records through a specific form and were filed on Excel. A total
of 534 patients were selected from the Pathology Department file in this institution,
however, 176 patients were excluded. 358 patients were included for Epidemiological
analysis and its clinical and pathological correlations were selected. 180 patients
were also selected for histological and immunohistochemical studies. The tumor progression
of these selected proteins mentioned before were analyzed. The Paraffin
blocks of these samples were treated by Microarray Tissue technique and its blades
subjected to immunohistochemistry to test the intensity of these proteins in tumor tissues.
The results of this analysis were correlated with clinicopathologic variables of
patients. Statistical analysis using the chi-frame Pearson test and analysis of midlife
by Kaplan-Meier curve was also utilized. P values < 0.05 were considered statistically
significant. The average age of our sample was 58.8 years and 51.7 % were
female. Alcohol consumption has increased by 1.71 time the risk of death by CCR
(p = 0.034) and tobacco consumption increased 2.7 times the chance of developing
tumors of high TNM stage (p = 0.001). Cancer patients had a family history of 3,833
times the chance of developing the CCR (p = 0.002). The expression of MMP-2 showed
a significant association with tumors of high TNM stage (p <0.046) and mortality
(p = 0.041). The ? VEGF expression had statistically significant correlation with high
TNM stage (p <0.009), degree of cell indifferentiation (p <0.025) and mortality (p
<0.035). Expressions of E-cadherin and beta-catetina demonstrated tumor linked to
high TNM stage (p = 0.0001) and Dukes? modified (p = 0.05), lesions in the rectum
(p = 0.03 and p = 0.007, respectively), smoking (p = 0.05) and indifferentiation (p =
0.001). The expression of Gal-3 showed statistical significance with high TNM stage
of patients (p = 0.01), smokers (p = 0.01), alcohol drinking (p = 0.03), indifferentiation
(p = 0.0001) and mortality (p = 0.0001). Based on the results, therefore, we could realize
that lifestyle and family history had correlation in the CCR prognosis, as well as
MMP-2 expression, MMP-9, VEGF alpha, E-cadherin, Beta-catenin and Galectin-3
were important prognostic markers in tumor progression in colorectal cancer.
Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/20590 |
Date | 31 August 2015 |
Creators | Lira, George Alexandre |
Contributors | 01847881459, http://lattes.cnpq.br/1903940945895093, Ara?jo, Aurigena Antunes de, 83806059420, http://lattes.cnpq.br/3531154240424211, Vieira, Jeymesson Raphael Cardoso, 02930177438, http://lattes.cnpq.br/6727125662817949, Ara?jo J?nior, Raimundo Fernandes de |
Publisher | Universidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS DA SA?DE, UFRN, Brasil |
Source Sets | IBICT Brazilian ETDs |
Language | Portuguese |
Detected Language | English |
Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
Rights | info:eu-repo/semantics/openAccess |
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