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p53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma

Rodrigues, Joana M. LU ; Hassan, May LU ; Freiburghaus, Catja LU ; Eskelund, Christian W. ; Geisler, Christian ; Räty, Riikka ; Kolstad, Arne ; Sundström, Christer ; Glimelius, Ingrid and Grønbæk, Kirsten , et al. (2020) In British Journal of Haematology
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
digital pathology, immunohistochemistry, mantle cell lymphoma, p53, targeted sequencing, TP53
in
British Journal of Haematology
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:85088874716
ISSN
0007-1048
DOI
10.1111/bjh.17023
language
English
LU publication?
yes
id
9e86314d-2db7-4593-b245-bd380996cf1f
date added to LUP
2020-08-10 12:16:55
date last changed
2020-08-19 08:50:29
@article{9e86314d-2db7-4593-b245-bd380996cf1f,
  abstract     = {<p>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.</p>},
  author       = {Rodrigues, Joana M. and Hassan, May and Freiburghaus, Catja and Eskelund, Christian W. and Geisler, Christian and Räty, Riikka and Kolstad, Arne and Sundström, Christer and Glimelius, Ingrid and Grønbæk, Kirsten and Kwiecinska, Anna and Porwit, Anna and Jerkeman, Mats and Ek, Sara},
  issn         = {0007-1048},
  language     = {eng},
  month        = {08},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {p53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma},
  url          = {http://dx.doi.org/10.1111/bjh.17023},
  doi          = {10.1111/bjh.17023},
  year         = {2020},
}