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Region Hovedstaden - en del af Københavns Universitetshospital
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Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP

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  • Pekka Peroja
  • Mette Ølgod Pedersen
  • Tuomo Mantere
  • Peter Nørgaard
  • Jenni Peltonen
  • Kirsi-Maria Haapasaari
  • Jan Böhm
  • Esa Jantunen
  • Taina Turpeenniemi-Hujanen
  • Katrin Rapakko
  • Peeter Karihtala
  • Ylermi Soini
  • Kaija Vasala
  • Outi Kuittinen
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Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with diverse outcomes. Concurrent translocation of MYC and BCL-2 and/or BCL-6, and concurrent immunohistochemical (IHC) high expression of MYC and BCL-2, have been linked to unfavorable treatment responses. TP53-mutated DLBCL has also been linked to worse outcome. Our aim was to evaluate the aforementioned issues in a cohort of 155 patients uniformly treated with R-CHOP-like therapies. We performed direct sequencing of TP53 exons 5, 6, 7 and 8 as well as fluorescence in-situ hybridization (FISH) of MYC, BCL-2 and BCL-6, and IHC of MYC, BCL-2 and BCL-6. In multivariate analysis, TP53 mutations in L3 and loop-sheet helix (LSH) associated with a risk ratio (RR) of disease-specific survival (DSS) of 8.779 (p = 0.022) and a RR of disease-free survival (DFS) of 10.498 (p = 0.011). In IHC analysis BCL-2 overexpression was associated with inferior DFS (p = 0.002) and DSS (p = 0.002). DLBCL with BCL-2 and MYC overexpression conferred inferior survival in all patients (DSS, p = 0.038 and DFS, p = 0.011) and in patients with non-GC phenotype (DSS (p = 0.013) and DFS (p = 0.010). Our results imply that in DLBCL, the location of TP53 mutations and IHC analysis of BCL-2 and MYC might have a role in the assessment of prognosis.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind8
Udgave nummer1
Sider (fra-til)14814
ISSN2045-2322
DOI
StatusUdgivet - 4 okt. 2018

ID: 56605361