Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

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...

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Veröffentlicht in:	Journal of clinical oncology Jg. 30; H. 28; S. 3452
Hauptverfasser:	Johnson, Nathalie A, Slack, Graham W, Savage, Kerry J, Connors, Joseph M, Ben-Neriah, Susana, Rogic, Sanja, Scott, David W, Tan, King L, Steidl, Christian, Sehn, Laurie H, Chan, Wing C, Iqbal, Javeed, Meyer, Paul N, Lenz, Georg, Wright, George, Rimsza, Lisa M, Valentino, Carlo, Brunhoeber, Patrick, Grogan, Thomas M, Braziel, Rita M, Cook, James R, Tubbs, Raymond R, Weisenburger, Dennis D, Campo, Elias, Rosenwald, Andreas, Ott, German, Delabie, Jan, Holcroft, Christina, Jaffe, Elaine S, Staudt, Louis M, Gascoyne, Randy D
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.10.2012
Schlagworte:	Adolescent Adult Aged Aged, 80 and over Antibodies, Monoclonal, Murine-Derived - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cyclophosphamide - therapeutic use Disease-Free Survival Doxorubicin - therapeutic use Female Gene Expression Profiling Humans Immunohistochemistry Lymphoma, Large B-Cell, Diffuse - drug therapy Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - mortality Male Middle Aged Prednisone - therapeutic use Prognosis Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-myc - genetics Rituximab Survival Rate Translocation, Genetic Vincristine - therapeutic use Young Adult
ISSN:	1527-7755, 1527-7755
Online-Zugang:	Weitere Angaben
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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.
AbstractList	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. 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.PURPOSEDiffuse 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.PATIENTS AND METHODSWe 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.RESULTSIn 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.CONCLUSIONAssessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
Author	Wright, George Slack, Graham W Braziel, Rita M Grogan, Thomas M Brunhoeber, Patrick Sehn, Laurie H Weisenburger, Dennis D Iqbal, Javeed Savage, Kerry J Rimsza, Lisa M Rogic, Sanja Delabie, Jan Holcroft, Christina Staudt, Louis M Rosenwald, Andreas Jaffe, Elaine S Gascoyne, Randy D Cook, James R Steidl, Christian Ott, German Tan, King L Meyer, Paul N Scott, David W Valentino, Carlo Tubbs, Raymond R Johnson, Nathalie A Lenz, Georg Campo, Elias Chan, Wing C Ben-Neriah, Susana Connors, Joseph M
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22851565$$D View this record in MEDLINE/PubMed
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Snippet	Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone...
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SubjectTerms	Adolescent Adult Aged Aged, 80 and over Antibodies, Monoclonal, Murine-Derived - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cyclophosphamide - therapeutic use Disease-Free Survival Doxorubicin - therapeutic use Female Gene Expression Profiling Humans Immunohistochemistry Lymphoma, Large B-Cell, Diffuse - drug therapy Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - mortality Male Middle Aged Prednisone - therapeutic use Prognosis Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-myc - genetics Rituximab Survival Rate Translocation, Genetic Vincristine - therapeutic use Young Adult
Title	Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
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