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Stratification by MYC expression has prognostic impact in MYC translocated B-cell lymphoma—Identifies a subgroup of patients with poor outcome

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@article{c00ad715baec4b239677e5cf3d19976e,
title = "Stratification by MYC expression has prognostic impact in MYC translocated B-cell lymphoma—Identifies a subgroup of patients with poor outcome",
abstract = "Objective: In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH). Methods: From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC). Results: MYC expression >75{\%} was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95{\%} CI 1.5-31), P = 0.004. OS: HR 4.3 (95{\%} CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide). Conclusion: These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.",
keywords = "B-cell, BCL2, MYC, WHO, fluorescent in situ hybridization, immunohistochemistry, lymphoma, prognostic, Immunohistochemistry, Translocation, Genetic, Lymphoma, B-Cell/diagnosis, Prognosis, Humans, Gene Expression Regulation, Neoplastic, Kaplan-Meier Estimate, Male, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Biomarkers, Tumor, Female, Proto-Oncogene Proteins c-myc/genetics, Neoplasm Staging, Oncogene Proteins, Fusion/genetics",
author = "Pedersen, {Mette {\O}lgod} and Gang, {Anne Ortved} and Linde, {Erik Clasen} and Breinholt, {Marie Fredslund} and Helle Knudsen and Nielsen, {Signe Ledou} and Poulsen, {Tim Svenstrup} and Klausen, {Tobias Wirenfeldt} and Estrid H{\o}gdall and Peter N{\o}rgaard",
note = "{\circledC} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2019",
doi = "10.1111/ejh.13219",
language = "English",
volume = "102",
pages = "395--406",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell Munksgaard",
number = "5",

}

RIS

TY - JOUR

T1 - Stratification by MYC expression has prognostic impact in MYC translocated B-cell lymphoma—Identifies a subgroup of patients with poor outcome

AU - Pedersen, Mette Ølgod

AU - Gang, Anne Ortved

AU - Linde, Erik Clasen

AU - Breinholt, Marie Fredslund

AU - Knudsen, Helle

AU - Nielsen, Signe Ledou

AU - Poulsen, Tim Svenstrup

AU - Klausen, Tobias Wirenfeldt

AU - Høgdall, Estrid

AU - Nørgaard, Peter

N1 - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019

Y1 - 2019

N2 - Objective: In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH). Methods: From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC). Results: MYC expression >75% was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5-31), P = 0.004. OS: HR 4.3 (95% CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide). Conclusion: These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.

AB - Objective: In patients with large B-cell lymphoma (LBCL) according to WHO, the prognostic significance of MYC translocation is still not sufficiently clarified. We therefore aimed to investigate whether prognostication could be improved in patients with MYC translocation positive LBCL by additional stratification according to MYC and BCL2 protein expression levels or MYC translocation partner gene as well as concurrent BCL2 and/or BCL6 translocation (DH). Methods: From an unselected consecutive cohort of >600 patients with LBCL investigated with fluorescent in situ hybridization (FISH), 64 patients were diagnosed with MYC translocation positive LBCL and included in the study. They were further investigated for supplemental translocations with FISH and MYC and BCL2 protein expression with immunohistochemistry (IHC). Results: MYC expression >75% was associated with both reduced progression-free survival (PFS) and overall survival (OS) (PFS: HR 6.8 (95% CI 1.5-31), P = 0.004. OS: HR 4.3 (95% CI 0.9-21), P = 0.05). Immunoglobulin (IG) MYC translocation partner gene was related to high MYC protein expression (P = 0.047) but was not prognostic for PFS (P = 0.8) or OS (P = 0.6). DH did not confer a worse outcome compared to MYC single hit (SH). These findings were confirmed in a comparable, independent validation cohort of 28 patients with MYC translocation positive LBCL. All patients included in the survival analyses were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOEP (R-CHOP + etoposide). Conclusion: These findings suggest that in patients with LBCL stratification by MYC protein expression level significantly improves the prognostic impact associated with MYC translocation.

KW - B-cell

KW - BCL2

KW - MYC

KW - WHO

KW - fluorescent in situ hybridization

KW - immunohistochemistry

KW - lymphoma

KW - prognostic

KW - Immunohistochemistry

KW - Translocation, Genetic

KW - Lymphoma, B-Cell/diagnosis

KW - Prognosis

KW - Humans

KW - Gene Expression Regulation, Neoplastic

KW - Kaplan-Meier Estimate

KW - Male

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Biomarkers, Tumor

KW - Female

KW - Proto-Oncogene Proteins c-myc/genetics

KW - Neoplasm Staging

KW - Oncogene Proteins, Fusion/genetics

U2 - 10.1111/ejh.13219

DO - 10.1111/ejh.13219

M3 - Journal article

VL - 102

SP - 395

EP - 406

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 5

ER -

ID: 56690324