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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References
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3 Potecá T, Potecá A, Sajin M et al. Biological prognostic parameters in gastric carcinomas. Chirurgia (Bucur). 2014;109:347-54
4 Thuler LC. Situação atual do câncer de estômago no Brasil.In: Eduardo Linhares, Laercio Lourenço, Takeshi Sano. Atualização em cancer gástrico, pg. 23-25. Tecmedd, São Paulo, 2005.
5 Dildey P, Bennett M. Pathology of benign, malignant and premalignant oesophageal and gastric tumors. In S. Michael Griffin, Simon A Raimes (eds). Upper Gastrointestinal Surgery. London. W.B.Saunders.2001.
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7 Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136:E359-E386
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9 Joyce W, Shams R, Nadia S. Prognostic Impact of Lymph Node Retrieval and Ratio in Gastric Cancer: a U.S. Single Center Experience. J Gastrointest Surg. 2013;17:2059-2066.
10 J.-T Hsu, C.-J. Lin, C.-M. Sung et al. Prognostic significance of examined lymph nodes in node-negative gastric adenocarcinoma. EJSO. 2013;39:1287-1293.
11 Chen GX, Zheng LH, Liu SY et al. rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy. World J Gastroenterol. 2011; 17: 4289-97.
11 Pelengaris S, Khan M. The barriers to cancer. Regulation of growth. In Pelengaris S, Khan M. The molecular Biology of Cancer. Oxford. Blackwell Publishing.2006.
12 Assumpção PP, Burbano RR. Genética e Cancer Gástrico.In: Eduardo Linhares, Laercio Lourenço, Takeshi Sano. Atualização em cancer gástrico, pg. 95-107. Tecmedd, São Paulo, 2005.
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14 Fondevila C, Metges JP, Pera M et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer. 2004; 90: 206-15.
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16 Masciari S, Dewanwala A, Stoffel EM et al. Gastric cancer in individuals with Li-Fraumeni syndrome.Genet Med. 2011; 13: 651-7.
17 Jang BG, Kim WH. Molecular pathology of gastric carcinoma. Pathobiology.2011; 78.302-10.
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19 André AR, Ferreira MV, Mota RM et al. Gastric adenocarcinomas and helicobacter pylori: correlation with p53 mutation and p27 immunoexpression. Cancer Epidemiol. 2010; 34: 618-25.
20 Buti L, Spooner E, Van der Veen AG et al. Helicobacter pylori Cytotoxin associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. ProcNatlSci USA. 2011; 108: 9238-43.
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25 Lan J, Xiong YY, Lin YX et al. Helicobacter pylori infection generated gastric cancer through p53-Rb tumor-supressor system mutation and telomerase reactivation. World J Gastroenterol. 2003;9:54-8
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Published
2015-10-01
How to Cite
FRADIQUE, Caldeira et al.
A oncoproteína mutante p53 como factor de apoio à decisão terapêutica no carcinoma gástrico.
Revista Portuguesa de Cirurgia, [S.l.], n. 34, p. 13 - 26, oct. 2015.
ISSN 2183-1165.
Available at: <https://revista.spcir.com/index.php/spcir/article/view/540>. Date accessed: 27 apr. 2024.
Section
Original Papers
