Mutant Pattern of p53 as a Feasible Predictor of Distant Metastasis Following Curative Gastrectomy for Advanced-stage Gastric Cancer.

Objective: The TP53 mutation is a poor prognostic factor for malignant tumors in a number of organs. The present study primarily aimed to clarify the impact of the mutant pattern of p53 on the prognosis and recurrence of gastric cancer. Methods: For this purpose, 519 patients who underwent radical gastrectomy for cancer were enrolled in the present study. Immunohistochemistry (IHC) was used to examine p53 expression in tissues and a three-stage classification system was used to divide the patient tissues into three groups according to the expression of p53: Heterogeneous (wild-type), absent and overexpression (mutant). Results: After 5 years of follow-up, recurrence and metastasis occurred in 38.7% of patients with stomach cancer, with a p53 mutant pattern in 48.4% of these patients. Patients with a p53 mutant pattern had lower recurrence-free and overall survival rates at 5 years compared with those who were p53 wild-type (P<0.001). It was found that the p53 pattern differed significantly (P<0.001) between the wild-type and mutant patterns, including the pN0 and pN+ gastric cancer subgroups (P<0.001 and P=0.014, respectively). The p53 mutant pattern was also significant in the determination of the recurrence-free survival of patients with progressive stomach cancer (P<0.0001). The 5-year overall survival rates were 71.7 and 36.2%, and the recurrence-free survival rates were 71.2 and 35.2% in the pN0 and pN+ groups, respectively (P<0.001). The mutant pattern of p53 was a significant prognostic factor for both distant metastasis [relative risk (RR)=2.881, P<0.001] and overall survival (RR=2.809, P<0.001) in the univariate Cox regression analysis. In the multivariate analysis, distant metastasis (RR=2.767, P<0.001) remained significant in the mutant pattern of p53 staining. After propensity score matching, 189 patients with a p53 wild-type and 189 patients with a p53 mutant pattern were extracted for analysis. The 5-year overall survival rate in patients with the p53 mutant pattern (n = 189) was worse than that in the patients with p53 wild-type (n = 189) and with significant differences (log-rank P<0.01). The study was statistically significant after Cox univariate and multivariate regression analysis, which revealed that the mutant pattern of p53 is an independent prognostic factor impacting distant metastases following curative gastrectomy for advanced-stage gastric cancer (p = 0.48).