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Multicenter Study
. 2013 Oct;98(10):1554-62.
doi: 10.3324/haematol.2013.086173. Epub 2013 May 28.

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Alexandra Valera  1 , Armando López-Guillermo, Teresa Cardesa-Salzmann, Fina Climent, Eva González-Barca, Santiago Mercadal, Iñigo Espinosa, Silvana Novelli, Javier Briones, José L Mate, Olga Salamero, Juan M Sancho, Leonor Arenillas, Sergi Serrano, Nadina Erill, Daniel Martínez, Paola Castillo, Jordina Rovira, Antonio Martínez, Elias Campo, Luis Colomo; Grup per l’Estudi dels Limfomes de Catalunya i Balears (GELCAB)
Affiliations
Multicenter Study

MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Alexandra Valera et al. Haematologica. 2013 Oct.

Abstract

MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

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Figures

Figure 1.
Figure 1.
Hematoxylineosin stain (x400), MYC immunohistochemistry (x400) and FISH in DLBCL cases (x1000). DLBCL with MYC protein expression in 82% of tumor cells and MYC rearrangements (1A–1C); MYC expression in 33% of cells in a case with MYC gains (1D–1F); MYC expression in 15% tumor cells and MYC amplifications (1G–1I).
Figure 2.
Figure 2.
Kaplan-Meier analysis of de novo DLBCL patients treated with immunochemotherapy with curative intent in different settings. (A) Progression-free survival (PFS) and (B) overall survival (OS) according to MYC gene alterations as assessed by FISH. (C) PFS and (D) OS of patients according to MYC expression as assessed by quantitative immunohistochemistry (IHC); a threshold of 10% was obtained by the Maxstat test. (E) PFS and (F) OS of patients according to MYC gene alterations and MYC expression.
Figure 3.
Figure 3.
Progression-free survival (A) and overall survival (B) of cases grouped according to MYC and BCL2 expression.
See this image and copyright information in PMC

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