Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer

摘要: Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations TP53, encoding tumour suppressor p53, International Lung Cancer Trial (IALT), a randomized trial adjuvant against observation. TP53 (exons 4-8) was sequenced 524 archived specimens IALT median follow-up 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ≤ 0.01 considered as significant. Mutations detected 221 (42%) had no effect (interaction between treatment: p = 0.17 Overall Survival (OS); 0.06 Disease-Free Interval, (DFS)). However, among mutations, outcome appeared worse treatment compared to observation arms (HR OS 1.36 (95% CI [0.97-1.31), 0.08; DFS 1.40 [1.01-1.95]), 0.04). When grouping into classes according predicted effects protein structure, tendency towards outcomes restricted "structure" affecting residues hydrophobic core that are not located at p53 protein-DNA interface death this class vs wild-type T53 1.66; 95% [1.10-2.52], 0.02). Overall, significant predictors chemotherapy, although specific structural may be associated upon treatment.