A oncoproteína mutante p53 como factor de apoio à decisão terapêutica no carcinoma gástrico
Abstract
Introdução – O carcinoma gástrico constitui a terceira causa oncológica de morte em Portugal. A metastização ganglionar, em particular a relação entre o número de gânglios ressecados e o número de gânglios metastizados, constitui o mais importante factor de prognóstico independente no carcinoma gástrico. A metastização das cadeias ganglionares distais assume um significado prognóstico pejorativo e condiciona as opções terapêuticas cirúrgicas e não cirúrgicas. Assim, na programação da terapêutica, torna-se importante encontrar marcadores da metastização ganglionar em geral e, em particular, da metastização das cadeias ganglionares distais. A proteína p53, produto do gene supressor tumoral TP53, funciona normalmente como um travão à replicação do ADN, como supressor da angiogénese e como factor desencadeante da apoptose. As mutações do gene TP53 constituem uma das alterações moleculares mais frequentes no carcinoma gástrico, levando à formação da proteína mutante p53. A sobre-expressão de p53 tem sido considerada factor de mau prognóstico e associada à metastização ganglionar.
Objectivos – O presente estudo procura determinar a relação entre a expressão de p53 e a metastização das cadeias ganglionares distais.
Material e Métodos – Foram estudados 50 doentes com carcinoma gástrico submetidos a cirurgia radical de intenção curativa, com linfadenectomia alargada. Foram estudados 1786 gânglios ressecados. Este número representa uma média de 35,7 gânglios ressecados por doente, uma das maiores a nível internacional. Correlacionou-se a expressão de p53 com a localização, dimensão, tipo histológico, invasão em profundidade, número de gânglios metastizados, metastização das cadeias ganglionares distais e estádio TNM.
Resultados – Em todos os parâmetros estudados, a proteína mutante p53 relacionou-se com indicadores de mau prognóstico. Em particular, demonstrou relação com significado estatístico (p = 0.019) com a metastização das cadeias ganglionares distais, ou seja, cadeias da segunda estação ganglionar ou mais distais.
Conclusão – A proteína mutante p53 é um bom indicador de prognóstico no adenocarcinoma gástrico. Ao identificar os tumores em risco de metastização das cadeias ganglionares distais é um elemento de apoio à decisão terapêutica, em particular no que respeita à extensão da linfadenectomia e à terapêutica neo-adjuvante e adjuvante.
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