Correlation analysis of TP53 missense mutations and p53 protein expression patterns in endometrial carcinoma

p53 abnormality (p53 abn) subtype is a critical category in endometrial carcinoma (EC) molecular classification, yet clinical diagnosis often relies solely on p53 immunohistochemistry (IHC) staining or TP53 gene sequencing. This study aimed to explore the correlation between TP53 genotype and p53 protein expression in EC with TP53 missense mutations, as well as the clinical and prognostic significance of their discordance. A total of 253 EC specimens from Zhejiang Cancer Hospital (January 2021-November 2023) were retrospectively collected; 103 cases with isolated TP53 missense mutations were screened via next-generation sequencing (NGS) and subjected to p53 IHC. Variant interpretation revealed that six mutations in six patients were of uncertain significance. Among the remaining patients, 54 (involving 36 variants) showed concordance between IHC phenotype and genotype: high frequency mutations such as R273H, Y220C, M237I, and V272L all exhibited mutant p53 expression, whereas V31I showed wild-type expression. Another 43 patients (involving 13 variants) displayed discordance between genotype and IHC phenotype. Clinicopathological comparison revealed that the discordant group was younger (<60 years) and dominated by non-aggressive histology (all P < 0.05). The discordant group showed better survival trends than the concordant group, with no statistically significant difference in disease-free survival (DFS) (P = 0.057). In conclusion, p53 expression is heterogeneous in EC with TP53 missense mutations; gene-protein discordance correlates with distinct clinicopathological features. Integrating genetic and protein detection results is recommended for risk stratification and individualized treatment.