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

Background: TP53 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: 76 bone marrow biopsy samples with different blast counts were analyzed. 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. Results: Both p53 expression and TP53 VAF showed a significant correlation with the myeloblast ratio (p<0.0001), however, p53 expres-sion was present in other cell lineages as well. 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. Conclusion: Strong (3+) p53 expression using a >= 10% cut-off value accurately predicts TP53 mutation but doesn't reveal the allelic state. The p53 expression is significantly influenced by myeloblast count, and histo-logical interpretation should consider the presence of intermixed non-neoplastic marrow cells with varying physiological p53 expression.