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

Joana M. Rodrigues, May Hassan, Catja Freiburghaus, Christian W. Eskelund, Christian Geisler, Riikka Räty, Arne Kolstad, Christer Sundström, Ingrid Glimelius, Kirsten Grønbæk, Anna Kwiecinska, Anna Porwit, Mats Jerkeman, Sara Ek

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)796-805
Antal sidor10
TidskriftBritish Journal of Haematology
Volym191
Nummer5
Tidigt onlinedatum2020 aug. 4
DOI
StatusPublished - 2020 dec.

Ämnesklassifikation (UKÄ)

  • Hematologi

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