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p53 is associated with high-risk and pinpoints TP53 missense mutations in mantle cell lymphoma
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- Rodrigues, Joana M. (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Hassan, May (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Freiburghaus, Catja (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Gronbae, K (författare)
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- (creator_code:org_t)
- 2020-08-04
- 2020
- Engelska 10 s.
- Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 191:5, s. 796-805
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- digital pathology
- immunohistochemistry
- mantle cell lymphoma
- p53
- targeted sequencing
- TP53
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- art (ämneskategori)
- ref (ämneskategori)
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- Rodrigues, Joana ...
- Hassan, May
- Freiburghaus, Ca ...
- Eskelund, Christ ...
- Geisler, Christi ...
- Räty, Riikka
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- Kolstad, Arne
- Sundström, Chris ...
- Glimelius, Ingri ...
- Grønbæk, Kirsten
- Kwiecinska, Anna
- Porwit, Anna
- Jerkeman, Mats
- Ek, Sara
- Gronbae, K
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