Linking p53 immunostaining to TP53 mutation status in patients with non-small cell lung cancer.

Abstract

TP53 mutations, which are prevalent in patients with non-small cell lung cancer (NSCLC), play a crucial role in carcinogenesis, are associated with poor prognosis ​and significantly contribute to resistance against key therapeutic options, such as chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors, and immunotherapy. However, sequencing of tissues from all patients to detect TP53 mutations is challenging. This study represents the first comprehensive analysis of the correlation between p53 immunohistochemical (IHC) staining and TP53 mutations in patients with NSCLC. This study aimed to examine the relationship between p53 IHC staining patterns and TP53 mutations using next-generation sequencing in 200 patients with NSCLCs. TP53 mutations were found in 122 patients (61%) and showed significant associations with sex, smoking status, and tumour mutation burden. A 20% cut-off for p53 IHC staining was optimal for predicting TP53 mutations, particularly missense variants. Correlation with TP53 mutation types revealed that 0% staining (complete loss pattern) was linked with truncating mutations, 1-19% staining (wild-type pattern) with wild-type TP53, and ≥20% staining (accumulation pattern) with missense mutations. These classifications were consistent with the findings of 184 patients (92%), whereas discrepancies were observed in 16 patients (8%), often owing to intratumoural heterogeneity. Patients with hotspot or critical region mutations exhibited higher concordance between p53 IHC and TP53 mutation status. In conclusion, p53 IHC staining is a reliable method for predicting TP53 mutations in patients with NSCLC and has significant implications for predicting prognosis and therapeutic responses.