Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL

Kerry J. Savage, Graham W. Slack, Anja Mottok, Laurie H. Sehn, Diego Villa, Roopesh Kansara, Robert Kridel, Christian Steidl, Daisuke Ennishi, King L. Tan, Susana Ben-Neriah, Nathalie A. Johnson, Joseph M. Connors, Pedro Farinha, David W. Scott, Randy D. Gascoyne

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Abstract

Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalinfixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater).With amedian follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7%vs 2.2%;P=.001). Patients with activatedB-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, inmultivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC+ BCL2+ DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies.

Original languageEnglish
Pages (from-to)2182-2188
Number of pages7
JournalBlood
Volume127
Issue number18
DOIs
Publication statusPublished - May 5 2016
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
Neurology
Central Nervous System
Immunohistochemistry
Recurrence
Cells
Biopsy
Vincristine
Microarrays
Prednisone
Gene expression
Paraffin
Doxorubicin
Cyclophosphamide
Assays
Lymphoma
B-Lymphocytes
Tissue
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Savage, K. J., Slack, G. W., Mottok, A., Sehn, L. H., Villa, D., Kansara, R., ... Gascoyne, R. D. (2016). Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. Blood, 127(18), 2182-2188. https://doi.org/10.1182/blood-2015-10-676700

Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. / Savage, Kerry J.; Slack, Graham W.; Mottok, Anja; Sehn, Laurie H.; Villa, Diego; Kansara, Roopesh; Kridel, Robert; Steidl, Christian; Ennishi, Daisuke; Tan, King L.; Ben-Neriah, Susana; Johnson, Nathalie A.; Connors, Joseph M.; Farinha, Pedro; Scott, David W.; Gascoyne, Randy D.

In: Blood, Vol. 127, No. 18, 05.05.2016, p. 2182-2188.

Research output: Contribution to journalArticle

Savage, KJ, Slack, GW, Mottok, A, Sehn, LH, Villa, D, Kansara, R, Kridel, R, Steidl, C, Ennishi, D, Tan, KL, Ben-Neriah, S, Johnson, NA, Connors, JM, Farinha, P, Scott, DW & Gascoyne, RD 2016, 'Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL', Blood, vol. 127, no. 18, pp. 2182-2188. https://doi.org/10.1182/blood-2015-10-676700
Savage KJ, Slack GW, Mottok A, Sehn LH, Villa D, Kansara R et al. Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. Blood. 2016 May 5;127(18):2182-2188. https://doi.org/10.1182/blood-2015-10-676700
Savage, Kerry J. ; Slack, Graham W. ; Mottok, Anja ; Sehn, Laurie H. ; Villa, Diego ; Kansara, Roopesh ; Kridel, Robert ; Steidl, Christian ; Ennishi, Daisuke ; Tan, King L. ; Ben-Neriah, Susana ; Johnson, Nathalie A. ; Connors, Joseph M. ; Farinha, Pedro ; Scott, David W. ; Gascoyne, Randy D. / Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. In: Blood. 2016 ; Vol. 127, No. 18. pp. 2182-2188.
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abstract = "Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called {"}double-hit lymphoma,{"} has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalinfixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS-IPI]), 34{\%} were low risk (0 to 1), 45{\%} were intermediate risk (2 to 3), and 21{\%} were high risk (4 or greater).With amedian follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2-year risk, 9.7{\%}vs 2.2{\%};P=.001). Patients with activatedB-cell or non-germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, inmultivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC+ BCL2+ DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies.",
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AU - Villa, Diego

AU - Kansara, Roopesh

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AU - Ennishi, Daisuke

AU - Tan, King L.

AU - Ben-Neriah, Susana

AU - Johnson, Nathalie A.

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