P53 immunohistochemistry is an ideal surrogate marker for TP53 mutation and a predictor of early metastasis in breast cancer: Real-world analysis

Abstract Purpose: TP53 mutation in breast cancer (BC) is associated with chemoresistance, endocrine resistance, and late recurrence, resulting in poor prognosis. Nuclear accumulation of p53 in immunohistochemistry (IHC) is a surrogate marker of TP53 mutation. We analyzed the frequency, type, and distribution of TP53 mutations in BCs and assessed the efficacy of p53 IHC as a surrogate marker of TP53 mutation. Methods: We collected 112 BC cases with the results of p53 IHC and next-generation sequencing (NGS). Results: Overexpression of p53 IHC was observed in 36 (32.1%), complete absence in 19 (17.0%), aberrant cytoplasmic staining in 1 (0.9%), and wild-type in 56 (50.0%) patients. The concordance rate of TP53mutation and p53 IHC was 88.4% in all BCs, 89.9% in luminal BC, and 86.0% in triple-negative BC (TNBC). TNBC, abnormal p53 IHC pattern, p53 IHC overexpression, neoadjuvant chemotherapy (NAC) history, TP53mutation, and high pre-treatment ki-67 labeling index (≥ 50%) were significantly associated with worse distant metastasis free survival (DMFS) and overall survival (OS) (p < 0.05). Pre-NAC clinical stage III was associated with worse DMFS but not OS. Multivariate analysis results showed history of NAC, TNBC, or p53 IHC overexpression as independent predictors of worse DMFS. Abnormal p53 IHC pattern and NAC history were independent predictors of worse OS. Conclusion: p53 IHC is a valid surrogate marker of TP53mutation of BC. Regardless of TP53 mutation, p53 IHC was associated with worse DMFS and OS and can be used as a biomarker to predict treatment resistance.