Mutation of TP53, translocation analysis and immunohistochemical expression of MYC, BCL-2 and BCL-6 in patients with DLBCL treated with R-CHOP View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Pekka Peroja, Mette 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

ABSTRACT

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. More... »

PAGES

14814

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-33230-3

DOI

http://dx.doi.org/10.1038/s41598-018-33230-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107306609

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30287880


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