Journal article
Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
Journal of clinical oncology, Vol.30(28), pp.3452-3459
10/01/2012
DOI: 10.1200/JCO.2011.41.0985
PMCID: PMC3454768
PMID: 22851565
Abstract
Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis.
We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation.
In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations.
Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
Details
- Title: Subtitle
- Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
- Creators
- Nathalie A Johnson - British Columbia Cancer Agency, Vancouver, British Columbia, CanadaGraham W SlackKerry J SavageJoseph M ConnorsSusana Ben-NeriahSanja RogicDavid W ScottKing L TanChristian SteidlLaurie H SehnWing C ChanJaveed IqbalPaul N MeyerGeorg LenzGeorge WrightLisa M RimszaCarlo ValentinoPatrick BrunhoeberThomas M GroganRita M BrazielJames R CookRaymond R TubbsDennis D WeisenburgerElias CampoAndreas RosenwaldGerman OttJan DelabieChristina HolcroftElaine S JaffeLouis M StaudtRandy D Gascoyne
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.30(28), pp.3452-3459
- DOI
- 10.1200/JCO.2011.41.0985
- PMID
- 22851565
- PMCID
- PMC3454768
- NLM abbreviation
- J Clin Oncol
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- Canadian Institutes of Health Research U01-CA-114778 / NCI NIH HHS U01 CA157581 / NCI NIH HHS U01 CA114778 / NCI NIH HHS
- Language
- English
- Date published
- 10/01/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984823119402771
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