RESUMEN
INTRODUCTION: The protein p73 is the first identified homolog of the tumor suppressor gene p53, but its function in tumor development has not been established. Indeed, the results regarding the p73 implication in colorectal cancers is still controversial. AIM: We investigated whether the p73 is implicated in colorectal cancer, whether the p73 expression is related to prognosis and whether the p73 expression is correlated with p21-ras or p53. MATERIALS AND METHODS: We performed a comparative immunohistochemical analysis of p73, p53, and p21ras proteins in primary colorectal tumor with matched normal mucosa and metastasis from 204 patients with colorectal cancer. We correlated these expressions with clinicopathologic variables and we compared the different profiles between nonmucinous carcinoma and mucinous carcinoma. RESULTS: In this study, we did not find any correlation between p73 expression, sex, age, site, differentiation and stage. Overexpression of p73 was significantly correlated with infiltrating growth pattern (P<0.0001) and nonmucinous carcinoma (P<0.0001). Furthermore, frequency and intensity of p73 expression were marquedly increased from normal mucosa (26%), to primary tumors (75%) and to metastasis (97%). Furthermore, expression of p73 was also correlated with shorter survival period. The prognostic significance of p73 expression remained, even after adjustment for the clinical and pathologic variables. The p73 expression was positively correlated only with p21ras expression (P<0.0001). CONCLUSIONS: All these findings prove that p73 expression should be considered as a valuable poor prognostic marker. Our data also suggest that TP73 gene may play a role in colorectal carcinoma development.
Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/diagnóstico , Proteínas de Unión al ADN/metabolismo , Membrana Mucosa/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/fisiopatología , Adenocarcinoma Mucinoso/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/fisiopatología , Neoplasias Colorrectales/secundario , Proteínas de Unión al ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Estadificación de Neoplasias , Proteínas Nucleares/genética , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Análisis de Supervivencia , Proteína Tumoral p73 , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: The p73 gene encodes a nuclear protein that is highy homologous to p53. p73 also shares some common functions with p53 protein indicating that p73 gene is a p53-like tumor suppressor. AIM: In this study, we examined by immunohistochemestry the p73 expression on 120 cases of colorectal carcinomas and evaluated its implication in carcinogenesis. METHODS: Retrospective study. RESULTS: The results show an increase of intensity and distribution of p73 in common adenocarcinoma from the normal mucosa, to primery tumors and to metastases. However, in mucinous adenocarcinomas, immunostaining of p73 decrease in primary tumor and completely diseappears in isolated cells and metastases compared with matched normal mucosa. These observations are further reinforced by the fact that in adenocarcinoma with mucinous component less than 50%, the positivity of p73 persist in well-differentiated areas and dramatically decreases or completely deseappears in mucinous areas. CONCLUSION: In conclusion, p73 would be a prognosic marker for the common adenocarcinomas and an ethiopathogenic factor for the mucinous subtype.