Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 191, Issue 5, Pages 796-805Publisher
WILEY
DOI: 10.1111/bjh.17023
Keywords
immunohistochemistry; p53; TP53; mantle cell lymphoma; digital pathology; targeted sequencing
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Funding
- European Community's Horizon 2020 Framework Programme for Research and Innovation [EU-H2020-MSCA-COFUND-2016-754299]
- Cancerfonden [2016/465, 2019/0309]
- Fru Berta Kamprad [FBKS-2018-7-(149)]
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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 withTP53missense 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 andTP53status 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 andTP53mutations on survival (hazard ratio of 3 center dot 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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