PMID- 23335369
OWN - NLM
STAT- MEDLINE
DCOM- 20130516
LR  - 20220408
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 121
IP  - 12
DP  - 2013 Mar 21
TI  - MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse 
      large B-cell lymphoma.
PG  - 2253-63
LID - 10.1182/blood-2012-06-435842 [doi]
AB  - MYC rearrangements occur in 5% to 10% of diffuse large B-cell lymphomas (DLBCL) 
      and confer an increased risk to cyclophosphamide, hydroxydaunorubicin, oncovin, 
      and prednisone (CHOP) and rituximab (R)-CHOP treated patients. We investigated 
      the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein 
      expression in a prospective randomized trial. Paraffin-embedded tumor samples 
      from 442 de novo DLBCL treated within the RICOVER study of the German High-Grade 
      Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using 
      immunohistochemistry and fluorescence in situ hybridization (FISH) to detect 
      protein expression and breaks of MYC, BCL2, and BCL6. Rearrangements of MYC, 
      BCL2, and BCL6 were detected in 8.8%, 13.5%, and 28.7%, respectively. Protein 
      overexpression of MYC (>40%) was encountered in 31.8% of tumors; 79.6% and 82.8% 
      of tumors expressed BCL2 and BCL6, respectively. MYC translocations, MYChigh, 
      BCL2high, and BCL6low protein expressions were associated with inferior survival. 
      In multivariate Cox regression modeling, protein expression patterns of MYC, BCL2 
      and BCL6, and MYC rearrangements were predictive of outcome and provided 
      prognostic information independent of the International Prognostic Index (IPI) 
      for overall survival and event-free survival. A combined immunohistochemical or 
      FISH/immunohistochemical score predicts outcome in DLBCL patients independent of 
      the IPI and identifies a subset of 15% of patients with dismal prognosis in the 
      high-risk IPI group following treatment with R-CHOP. Registered at 
      http://www.cancer.gov/clinicaltrials: RICOVER trial of the DSHNHL is NCT 
      00052936.
FAU - Horn, Heike
AU  - Horn H
AD  - Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete 
      Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
FAU - Ziepert, Marita
AU  - Ziepert M
FAU - Becher, Claudia
AU  - Becher C
FAU - Barth, Thomas F E
AU  - Barth TF
FAU - Bernd, Heinz-Wolfram
AU  - Bernd HW
FAU - Feller, Alfred C
AU  - Feller AC
FAU - Klapper, Wolfram
AU  - Klapper W
FAU - Hummel, Michael
AU  - Hummel M
FAU - Stein, Harald
AU  - Stein H
FAU - Hansmann, Martin-Leo
AU  - Hansmann ML
FAU - Schmelter, Christopher
AU  - Schmelter C
FAU - Moller, Peter
AU  - Moller P
FAU - Cogliatti, Sergio
AU  - Cogliatti S
FAU - Pfreundschuh, Michael
AU  - Pfreundschuh M
FAU - Schmitz, Norbert
AU  - Schmitz N
FAU - Trumper, Lorenz
AU  - Trumper L
FAU - Siebert, Reiner
AU  - Siebert R
FAU - Loeffler, Markus
AU  - Loeffler M
FAU - Rosenwald, Andreas
AU  - Rosenwald A
FAU - Ott, German
AU  - Ott G
CN  - German High-Grade Non-Hodgkin Lymphoma Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00052936
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130118
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (BCL6 protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 5J49Q6B70F (Vincristine)
RN  - 80168379AG (Doxorubicin)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - VB0R961HZT (Prednisone)
RN  - CHOP protocol
SB  - IM
CIN - Blood. 2013 Mar 21;121(12):2165-6. PMID: 23520325
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Murine-Derived/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/genetics
MH  - Cyclophosphamide/therapeutic use
MH  - DNA-Binding Proteins/*genetics/physiology
MH  - Doxorubicin/therapeutic use
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Genes, myc/*genetics/physiology
MH  - Humans
MH  - Lymphoma, Large B-Cell, Diffuse/*diagnosis/drug therapy/*genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Prednisone/therapeutic use
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-bcl-2/*genetics/physiology
MH  - Proto-Oncogene Proteins c-bcl-6
MH  - Randomized Controlled Trials as Topic
MH  - Rituximab
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Vincristine/therapeutic use
EDAT- 2013/01/22 06:00
MHDA- 2013/05/17 06:00
CRDT- 2013/01/22 06:00
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
AID - S0006-4971(20)47291-X [pii]
AID - 10.1182/blood-2012-06-435842 [doi]
PST - ppublish
SO  - Blood. 2013 Mar 21;121(12):2253-63. doi: 10.1182/blood-2012-06-435842. Epub 2013 
      Jan 18.