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MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma
- Source :
- Blood. 121(12)
- Publication Year :
- 2013
-
Abstract
- 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.
- Subjects :
- Male
Genes, myc
CHOP
Biochemistry
Antibodies, Monoclonal, Murine-Derived
0302 clinical medicine
International Prognostic Index
immune system diseases
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Aged, 80 and over
0303 health sciences
medicine.diagnostic_test
Hematology
Middle Aged
BCL6
Prognosis
3. Good health
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Treatment Outcome
Proto-Oncogene Proteins c-bcl-2
Vincristine
030220 oncology & carcinogenesis
Proto-Oncogene Proteins c-bcl-6
Rituximab
Female
Lymphoma, Large B-Cell, Diffuse
medicine.drug
Immunology
03 medical and health sciences
medicine
Biomarkers, Tumor
Humans
Cyclophosphamide
Survival analysis
030304 developmental biology
Aged
business.industry
Cell Biology
medicine.disease
Survival Analysis
Lymphoma
Doxorubicin
Cancer research
Prednisone
business
Diffuse large B-cell lymphoma
Fluorescence in situ hybridization
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 121
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....901181e02b5d908b3971068ae940108a