Correlation of P53 expression and TP53 mutation in stage I lung adenocarcinoma and the predictive value for postoperative recurrence within 5 years

OBJECTIVE: This study seeks to explore the correlation between P53 expression and TP53 mutations in stage I lung adenocarcinoma, while also assessing their predictive value for postoperative recurrence within 5 years. METHODS AND RESULTS: Next-generation sequencing (NGS) of the TP53 gene and immunohistochemistry (IHC) for P53 protein were performed on formalin-fixed paraffin-embedded (FFPE) tissue samples from 191 patients diagnosed with stage I lung adenocarcinoma. Two thresholds for P53 overexpression were established: 40% for predicting TP53 mutations, determined through ROC curve analysis, and 60% for predicting recurrence, utilizing X-tile software. We defined P53 mutant expression as either overexpression (>40%) or null-expression (0%) and P53 aberrant expression as overexpression (>60%). A significant association was found between P53 mutant expression and TP53 mutations (p < 0.001), demonstrating 87.9% sensitivity and 98.4% specificity, with a perfect concordance (κ = 0.882). No significant differences in survival outcomes were observed among the distinct P53 mutant expression patterns and TP53 mutation types. In survival analysis, pTNM stage, histopathology grade, P53 aberrant expression and TP53 missense mutation were recognized as independent prognostic factors in stage I lung adenocarcinoma. CONCLUSIONS: Based on our study's criteria, P53 mutant expression may serve as a surrogate marker for TP53 mutations, while P53 aberrant expression, along with TP53 missense mutation could potentially predict postoperative recurrence within five years for patients with stage I lung adenocarcinoma. The biomarkers of TP53 mutation, P53 mutant expression and P53 aberrant expression present opportunities for enhanced risk stratification and the formulation of personalized treatment strategies.