Correlative assessment of p53 immunostaining patterns and TP53 mutation status by next-generation sequencing in lung adenocarcinoma (LUAD).
A ≥40% cutoff for 3+ p53 nuclear staining predicts TP53 mutation with high accuracy.
Correlative assessment of p53 immunostaining patterns and TP53 mutation status by next-generation sequencing in lung adenocarcinoma (LUAD).
This study aimed to evaluate the diagnostic accuracy of p53 immunohistochemistry (immunohistochemistry) as a rapid and cost-effective alternative to next-generation sequencing (next-generation sequencing) for TP53 mutation detection in lung adenocarcinoma patients.
A multicentre cohort of 221 lung adenocarcinoma patients was analysed.
40% cutoff for 3+ nuclear staining correctly predicts TP53 mutation status
p53 immunohistochemistry demonstrated high concordance with TP53 mutation status, achieving an overall accuracy of 91.40% (κ = 0.83).
Complete p53 absence or cytoplasmic expression strongly correlated with truncating mutations (92.31% concordance), while missense mutations were linked to nuclear overexpression.
TP53-mutant tumours exhibited distinct molecular profiles, including increased frequencies of RB1, MET, ERBB2, MYC and PTCH1 mutations, alongside reduced STK11 comutations.
p53 immunohistochemistry, particularly using a ≥40% cut-off at 3+ intensity, is an accurate and accessible surrogate for TP53 mutation detection in lung adenocarcinoma patients.
This method facilitates rapid molecular stratification, optimal resource utilization and informed prognostic and therapeutic decision-making in routine pathology practice.