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Authors
Advisor(s)
Abstract(s)
O cancro colorretal é o terceiro cancro mais comum a nível mundial e o segundo mais
mortal, registando-se um aumento crescente do número de casos. Em Portugal, este tipo
de cancro ocupa o primeiro lugar em termos de incidência, com baixa sobrevida aos 5
anos.
Apesar dos avanços em termos de diagnóstico precoce e tratamento, nas últimas décadas,
não se conseguiu dar uma resposta eficaz a este problema.
Os fatores de prognóstico que se dispõe actualmente são insuficientes (estadiamento
TNM, presença/ausência de doença residual pós-cirurgia, classificação histológica,
presença/ausência de invasão ganglionar e/ou metástases à distância). Como tal, torna-se
necessário investigar a existência de novos marcadores moleculares que sirvam como
fatores de prognóstico e como elementos facilitadores da decisão terapêutica.
A proteína p53 regula vários processos celulares como a apoptose, a reparação do ADN e o
funcionamento do ciclo celular. Neste sentido, a sua mutação condiciona estas funções
reguladoras e confere-lhe um papel essencial na carcinogénese.
Este marcador molecular tem sido alvo de investigação científica, nos últimos anos, com o
intuito de se perceber qual o seu valor prognóstico no cancro colorretal. Apesar do
investimento nesta área, os resultados da literatura existente ainda são controversos.
Objetivos:
1) Detetar através do método de coloração imunohistoquímica a expressão da
oncoproteína p53.
2) Analisar a expressão imunohistoquímica da oncoproteína p53 e dos parâmetros
clínico-histopatológicos em estudo.
3) Determinar o valor prognóstico da expressão da proteína p53 em doentes com
cancro colorretal e a sua correlação com os parâmetros clínico-histopatológicos:
grau de diferenciação, localização e prognóstico.
Métodos:
Estudo clínico-patológico retrospectivo realizado nas peças cirúrgicas de 32 doentes, com
mais de 50 anos, que foram submetidos a uma resseção cirúrgica do cancro do colorretal,
no Serviço de Cirurgia do Centro Hospitalar Universitário da Cova da Beira, na Covilhã,
entre 2002-2005. As amostras foram processadas histologicamente no serviço de Anatomia Patológica do
mesmo hospital. Foram, de seguida, diagnosticadas de acordo com o tipo histológico, grau
de diferenciação e estadiamento TMN. Posteriormente, foram consideradas de acordo com
a intensidade e percentagem de células marcadas imunohistoquímicamente pela
oncoproteína p53.
Os dados foram analisados estatisticamente considerando-se um p-value<0,05 e pvalue<0,1, como estatisticamente significativos.
Resultados:
A “expressão imunohistoquímica de células marcadas pela oncoproteína p53” encontrouse associada a "estadiamentos TNM" mais avançados (p-value<0,05) e a
"adenocarcinomas pouco diferenciados" (p-value<0,1). Os "adenocarcinomas bem
diferenciados" foram estatisticamente associados à ausência de marcação pela
oncoproteína p53 (p-value<0,05). Não se verificaram resultados estatisticamente
significativos entre a “expressão imunohistoquímica de células marcadas pela
oncoproteína p53” e a “localização do tumor”. Os resultados também não foram
significativos em relação ao "prognóstico", apesar da análise da frequência indicar que a
marcação com o p53 está associada a menor sobrevida.
Conclusão:
Apesar das potencialidades, ainda não é possível atribuir valor prognóstico ao p53.
Deverão ser efectuados estudos mais representativos e que associem o conhecimento da
genética, bem como outros marcadores.
Colorectal cancer is the third most common cancer worldwide and the second most deadly, with increasing number of cases. In Portugal, this type of cancer ranks first in terms of incidence, with low survival at 5 years. Despite advances in early diagnosis and treatment, the problem has not been effectively addressed, in recent decades. The currently available prognostic factors are insufficient (TNM staging system, presence/absence of post-surgery residual disease, histological classification, presence/absence of lymph nodes invasion and distant metastases). So, it is necessary to investigate the existence of new molecular markers that can be used as prognostic factors and as facilitating elements of the therapeutic decision. The p53 protein regulates various cellular processes such as apoptosis, DNA repair and the proper functioning of cell cycle. In this sense, p53 mutation changes its regulatory functions and plays an essential role in carcinogenesis. This molecular marker has been the target of scientific research in recent years, aiming to understand its prognostic value in colorectal cancer. Despite the investment in this area, the results of the existing literature still are controversial. Objectives: 1) Detect through immunohistochemical staining the oncoprotein p53 expression. 2) Analyse the immunohistochemical staining of the oncoprotein p53 and the clinicalhistopathological parameters of this study. 3) Determine the prognostic value of p53 expression in patients with colorectal cancer and its correlations with clinical-histopathological parameters: histological differentiation degree, location and prognostic. Methods: Retrospective clinical-pathological study accomplished on the surgical samples of 32 patients, with more than 50 years, that were submitted to surgical resection of the colorectal cancer in the Department of Surgery of Centro Hospitalar Universitário da Cova da Beira, in Covilhã, between 2002-2005. The samples were histologically processed in the Department of Pathologic Anatomy of the hospital. Then they were categorized according to the histological type, differentiation degree and TNM staging system. Lastly, there were considerate according with the intensity and percentage of the immunohistochemical staining by the oncoprotein p53. The data were statistically analysed by taking into consideration a p-value<0,05 and pvalue<0.1 as statistically significant. Results: The “expression of immunohistochemical cells stained by the oncoprotein p53” was associated with advanced "TNM staging system" (p-value<0.05) and "poorly differentiated adenocarcinomas" (p-value <0.1). "Well differentiated adenocarcinomas" were statistically associated with lack expression of the p53 oncoprotein (p-value<0.05). There were no significant results between “expression of immunohistochemical cells stained by the oncoprotein p53” and “tumor localization”. Although frequency analysis indicated that p53 expression is associated with shorter survival, the results were also not significant about the "prognostic of patients". Conclusion: Despite the potentialities, it is not possible to assign prognostic value to p53, yet. More representative studies, associated with knowledge of genetics and other markers should be performed.
Colorectal cancer is the third most common cancer worldwide and the second most deadly, with increasing number of cases. In Portugal, this type of cancer ranks first in terms of incidence, with low survival at 5 years. Despite advances in early diagnosis and treatment, the problem has not been effectively addressed, in recent decades. The currently available prognostic factors are insufficient (TNM staging system, presence/absence of post-surgery residual disease, histological classification, presence/absence of lymph nodes invasion and distant metastases). So, it is necessary to investigate the existence of new molecular markers that can be used as prognostic factors and as facilitating elements of the therapeutic decision. The p53 protein regulates various cellular processes such as apoptosis, DNA repair and the proper functioning of cell cycle. In this sense, p53 mutation changes its regulatory functions and plays an essential role in carcinogenesis. This molecular marker has been the target of scientific research in recent years, aiming to understand its prognostic value in colorectal cancer. Despite the investment in this area, the results of the existing literature still are controversial. Objectives: 1) Detect through immunohistochemical staining the oncoprotein p53 expression. 2) Analyse the immunohistochemical staining of the oncoprotein p53 and the clinicalhistopathological parameters of this study. 3) Determine the prognostic value of p53 expression in patients with colorectal cancer and its correlations with clinical-histopathological parameters: histological differentiation degree, location and prognostic. Methods: Retrospective clinical-pathological study accomplished on the surgical samples of 32 patients, with more than 50 years, that were submitted to surgical resection of the colorectal cancer in the Department of Surgery of Centro Hospitalar Universitário da Cova da Beira, in Covilhã, between 2002-2005. The samples were histologically processed in the Department of Pathologic Anatomy of the hospital. Then they were categorized according to the histological type, differentiation degree and TNM staging system. Lastly, there were considerate according with the intensity and percentage of the immunohistochemical staining by the oncoprotein p53. The data were statistically analysed by taking into consideration a p-value<0,05 and pvalue<0.1 as statistically significant. Results: The “expression of immunohistochemical cells stained by the oncoprotein p53” was associated with advanced "TNM staging system" (p-value<0.05) and "poorly differentiated adenocarcinomas" (p-value <0.1). "Well differentiated adenocarcinomas" were statistically associated with lack expression of the p53 oncoprotein (p-value<0.05). There were no significant results between “expression of immunohistochemical cells stained by the oncoprotein p53” and “tumor localization”. Although frequency analysis indicated that p53 expression is associated with shorter survival, the results were also not significant about the "prognostic of patients". Conclusion: Despite the potentialities, it is not possible to assign prognostic value to p53, yet. More representative studies, associated with knowledge of genetics and other markers should be performed.
Description
Keywords
Cancro Colorretal Grau de Diferenciação Histológica Localização P53 Prognóstico