TP53 apoptosis biomarkers in breast cancer.

PMID 41135852 | DOI 10.1016/j.cca.2025.120678 · Clinica chimica acta; international journal of clinical chemistry · 2026 · View on PubMed ↗

Tumor protein p53 (TP53) plays a crucial role in regulating apoptosis and maintaining genomic stability, making TP53-mediated cell death an important diagnostic marker for breast cancer therapy. This review compiles laboratory methodologies for the application of TP53 apoptosis assays to standard clinical specimens. Modern diagnostic techniques enhance the management of formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) samples, as well as liquid biopsy systems, to preserve nucleic acid integrity for subsequent analysis. Analytical platforms, including targeted next-generation sequencing (NGS), droplet digital polymerase chain reaction (ddPCR), and multiplex reverse transcription (RT), exhibit high sensitivity, achieving detection limits below 0.5 % variant allele fraction (VAF), and are supported by orthogonal confirmation methods. Immunohistochemical (IHC) assays employing proteins such as p53, BCL2-associated X protein (BAX), and cleaved caspase-3 provide quantifiable indicators of apoptosis in standard pathological sample. Integrating genomic variants with pathway-level signatures enhances the clinical interpretation of prognosis, therapeutic decision-making, and monitoring of minimal residual disease (MRD). Achieving laboratory accreditation necessitates the implementation of standardized preanalytical controls, validation of methods with clearly defined analytical performance criteria, and establishment of consistent reporting systems. In metastatic disease cases, there is an 87 % concordance between tissue and circulating tumor DNA (ctDNA) across various platforms, supporting its clinical application. This approach translates TP53-apoptosis data from research tools into validated tests for clinical application in breast cancer treatment and future research initiatives.