Mutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer

Abstract

Background. TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. Methods. Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semiquantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). Results. Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. Conclusions. Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.