Real-world Comparison of P53 Immunohistochemistry and TP53 Mutation Analysis Using Next-generation Sequencing

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• TP53 mutations in breast cancer (BC) correlate with resistance to therapies and poor prognosis.
• Nuclear accumulation of p53 via immunohistochemistry (IHC) serves as a surrogate for TP53 mutations.

Purpose of the Study:

• To investigate the frequency, types, and distribution of TP53 mutations in BC.
• To evaluate the effectiveness of p53 IHC as a surrogate marker for TP53 mutations.

Main Methods:

• Analysis of p53 IHC and next-generation sequencing (NGS) data from 112 BC cases.
• Assessment of concordance between TP53 mutation status and p53 IHC patterns.

Main Results:

• P53 IHC over-expression was found in 32.1% of cases; concordance with TP53 mutation was 88.4%.
• Triple-negative BC (TNBC), abnormal p53 IHC, and p53 over-expression were associated with worse survival outcomes.
• Neoadjuvant chemotherapy (NAC) history, TNBC, and p53 IHC over-expression independently predicted worse distant metastasis-free survival (DMFS).

Conclusions:

• P53 IHC is a validated surrogate marker for TP53 mutations in breast cancer.
• Abnormal p53 accumulation, irrespective of TP53 mutation status, indicates poorer prognosis and can predict chemoresistance.