RESUMEN
BACKGROUND: We examined the association of one linked GC/AT polymorphism at p73 with the risk of colorectal cancer. AIM: In this study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and loss of heterozygosity, protein expression, or clinicopathologic variables. MATERIALS AND METHODS: The p73 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 150 Tunisian patients with colorectal cancer and in 204 healthy control subjects. Immunohistochemistry was performed on normal mucosa, primary tumor, and metastasis. RESULTS: The frequencies of the genotypes were 52% for wild-type (GC/GC), 31% for heterozygotes (GC/AT), and 17% for variants(AT/AT) in patients, and 54%, 35%, and 11% in controls, respectively. There were no significant differences of the frequencies of the 3 genotypes between the patients and controls (P=0.11). We did not find any relationship of the genotypes with clinicopathologic features of patients. We found that patients with the GC/GC genotype had a significantly more favorable clinical outcome than the patients with the AT variants (AT/AT or GC/AT genotype). There were no significant difference between tumoral immunostaining and p73 polymorphism (P=0.16) but we found that the samples carrying the AT allele showed a tendency to be more stained in tumor. No loss of heterozygosity was observed at p73 locus. Our results suggest that the AT/AT genotype is significantly associated with poor prognosis in colorectal cancer. All these findings suggest that p73 polymorphism analysis may provide useful prognostic information for colorectal cancer patients.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Unión al ADN , Inmunohistoquímica , Mucosa Intestinal/ultraestructura , Proteínas Nucleares/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Isoformas de Proteínas/genética , Proteínas Supresoras de Tumor , Estudios de Casos y Controles , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/genética , Femenino , Estudios de Asociación Genética , Humanos , Inmunohistoquímica/métodos , Mucosa Intestinal/fisiopatología , Estimación de Kaplan-Meier , Pérdida de Heterocigocidad , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Proteína Tumoral p73 , Proteínas Supresoras de Tumor/genética , TúnezRESUMEN
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.