Exploring p53 protein expression and its link to TP53 mutation in myelodysplasia‐related malignancies—Interpretive challenges and potential field of applications

Abstract

AimsTP53 alterations have a significant prognostic effect in myeloid neoplasms. Our objective was to investigate the TP53 gene mutation status, p53 protein expression and their relationship in dysplasia‐related myeloid neoplasms with varying levels of myeloblast counts.Methods and resultsA total of 76 bone marrow biopsy samples with different blast counts were analysed. Total and strong (3+) p53 expression was determined. Dual immunohistochemical staining was performed to determine the cell population associated with p53 expression. NGS analysis was performed using the Accel‐Amplicon Comprehensive TP53 panel. Both p53 expression and TP53 VAF showed a significant correlation with the myeloblast ratio (P < 0.0001); however, p53 expression was also present in other cell lineages. The VAF value exhibited a significant correlation with p53 expression. A high specificity (0.9800) was observed for TP53 mutation using the ≥ 10% strong (3+) p53 cut‐off value, although the sensitivity (0.4231) was low.ConclusionsStrong (3+) p53 expression using a ≥ 10% cut‐off value accurately predicts TP53 mutation but does not reveal the allelic state. The p53 expression is significantly influenced by myeloblast count, and histological interpretation should consider the presence of intermixed non‐neoplastic marrow cells with varying physiological p53 expression.