【Objective】To investigate the clinicopathological relevance and prognostic value of p53 expression in Ewing sarcoma.【Methods】A total of 108 cases of Ewing sarcoma patients were retrospectively analyzed. p53 expression were detected by immunohistochemistry and the prognostic effect of p53 expression on clinicopathologic parameters and overall survival were analyzed by chi-squaretest

Kaplan-Meier curves

log-rank test and Cox regression model.【Results】p53 was positively expressed in 17 (15.7%) patients. Positive expression of p53 correlated significantly with some advanced clinicopathologic parameters including metastatic stage at initial diagnosis (=0.007) and venous/nerve invasion (=0.023). Moreover

positive expression of p53 was significantly related to poor overall survival of patients with Ewing sarcoma by log-rank test (<0.001) and univariate analysis (<0.001). Then

we constructed a novel molecular staging system which combined p53 expression and clinical stage classification at diagnosis and further refined the prognostic ability of conventional clinical staging. Finally

a multivariate Cox regression analysis indicated that p53 and initial stage were the most significant independent predictors of survival (<0.001 and <0.001

respectively).【Conclusions】p53 expression was an independent adverse prognostic factor for overall survival in patients with Ewing sarcoma. Integrating p53 into clinical staging significantly enhanced prognostic stratification.