Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Exploring p53 Protein Expression and Its Link to TP53 Mutation in Myelodysplasia-Related Malignancies - Interpretive Challenges and Potential Field of Applications

Judit Bedekovics
* ,
Kristóf Madarász
ORCID logo ,
Attila Mokánszki
ORCID logo ,
Sarolta Molnár
,
Ágnes Mester
,
Zsófia Miltényi
,
Gábor Méhes
Version 1 : Received: 31 August 2023 / Approved: 1 September 2023 / Online: 4 September 2023 (07:23:19 CEST)

A peer-reviewed article of this Preprint also exists.

Bedekovics, J.; Madarász, K.; Mokánszki, A.; Molnár, S.; Mester, Á.; Miltényi, Z.; Méhes, G. Exploring P53 Protein Expression and Its Link to TP53 Mutation in Myelodysplasia‐related Malignancies—Interpretive Challenges and Potential Field of Applications. Histopathology 2024, doi:10.1111/his.15185. Bedekovics, J.; Madarász, K.; Mokánszki, A.; Molnár, S.; Mester, Á.; Miltényi, Z.; Méhes, G. Exploring P53 Protein Expression and Its Link to TP53 Mutation in Myelodysplasia‐related Malignancies—Interpretive Challenges and Potential Field of Applications. Histopathology 2024, doi:10.1111/his.15185.

Abstract

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 re-lationship 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.

Keywords

p53 expression; TP53 mutation; myelodysplasia; myeloblast; bone marrow

Subject

Medicine and Pharmacology, Pathology and Pathobiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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