p53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma.
TP53
digital pathology
immunohistochemistry
mantle cell lymphoma
p53
targeted sequencing
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
03
06
2020
accepted:
12
07
2020
pubmed:
5
8
2020
medline:
24
3
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
Survival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy-based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high-risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients with TP53 missense mutations and the prognostic impact of overexpression and mutations in a Swedish population-based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 and TP53 status among 137 cases divided over the two-cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression and TP53 mutations on survival (hazard ratio of 3·1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population-based setting.
Identifiants
pubmed: 32748433
doi: 10.1111/bjh.17023
pmc: PMC7754513
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
796-805Subventions
Organisme : European Community's Horizon 2020 Framework Programme for Research and Innovation
ID : EU-H2020-MSCA-COFUND-2016-754299
Organisme : Cancerfonden
ID : 2016/465
Organisme : Cancerfonden
ID : 2019/0309
Organisme : Fru Berta Kamprads Stiftelse
ID : FBKS-2018-7-(149)
Informations de copyright
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
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