PMID- 30737994
OWN - NLM
STAT- MEDLINE
DCOM- 20191114
LR  - 20191114
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 102
IP  - 5
DP  - 2019 May
TI  - Stratification by MYC expression has prognostic impact in MYC translocated B-cell 
      lymphoma-Identifies a subgroup of patients with poor outcome.
PG  - 395-406
LID - 10.1111/ejh.13219 [doi]
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.
CI  - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Pedersen, Mette Olgod
AU  - Pedersen MO
AUID- ORCID: 0000-0002-8561-9421
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Gang, Anne Ortved
AU  - Gang AO
AD  - Department of Hematology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Clasen-Linde, Erik
AU  - Clasen-Linde E
AD  - Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
FAU - Breinholt, Marie Fredslund
AU  - Breinholt MF
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Knudsen, Helle
AU  - Knudsen H
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Nielsen, Signe Ledou
AU  - Nielsen SL
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Poulsen, Tim Svenstrup
AU  - Poulsen TS
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Klausen, Tobias Wirenfeldt
AU  - Klausen TW
AD  - Department of Hematology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Hogdall, Estrid
AU  - Hogdall E
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
FAU - Norgaard, Peter
AU  - Norgaard P
AD  - Department of Pathology, Herlev and Gentofte Hospital, Herlev, Denmark.
LA  - eng
GR  - Krista og Viggo Petersens fond/
GR  - Dansk Kraeftforsknings Fond/
PT  - Journal Article
DEP - 20190306
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins c-myc)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - *Biomarkers, Tumor
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Lymphoma, B-Cell/diagnosis/*genetics/*mortality/therapy
MH  - Male
MH  - Neoplasm Staging
MH  - Oncogene Proteins, Fusion/genetics/metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-myc/*genetics/metabolism
MH  - *Translocation, Genetic
OTO - NOTNLM
OT  - B-cell
OT  - BCL2
OT  - MYC
OT  - WHO
OT  - fluorescent in situ hybridization
OT  - immunohistochemistry
OT  - lymphoma
OT  - prognostic
EDAT- 2019/02/10 06:00
MHDA- 2019/11/15 06:00
CRDT- 2019/02/10 06:00
PHST- 2018/10/22 00:00 [received]
PHST- 2019/01/26 00:00 [revised]
PHST- 2019/01/28 00:00 [accepted]
PHST- 2019/02/10 06:00 [pubmed]
PHST- 2019/11/15 06:00 [medline]
PHST- 2019/02/10 06:00 [entrez]
AID - 10.1111/ejh.13219 [doi]
PST - ppublish
SO  - Eur J Haematol. 2019 May;102(5):395-406. doi: 10.1111/ejh.13219. Epub 2019 Mar 6.