Real-world routine diagnostic molecular analysis for TP53 mutational status is recommended over p53 immunohistochemistry in B-cell lymphomas
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin, vol. 485, pp. 643–654
Abstract
Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1-50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3-88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7-74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status.
Authors 19
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands. l.m.de_haan@lumc.nl
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Pathology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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Affiliation as printed
Department of Pathology, Haga Hospital, The Hague, The Netherlands
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Affiliation as printed
Department of Pathology, Alrijne Hospital, Leiden, The Netherlands
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Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum
Affiliation as printed
Department of Pathology, Haaglanden Medical Centrum, The Hague, The Netherlands
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Affiliation as printed
Department of Pathology, Groene Hart Ziekenhuis, Gouda, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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University Medical Center Groningen · Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, L1-Q, P.O. box 9600, 2300RC, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
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