Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

被引：760

作者：

Johnson, Nathalie A. ^{[2
]}

Slack, Graham W. ^{[1
]}

Savage, Kerry J. ^{[1
]}

Connors, Joseph M. ^{[1
]}

Ben-Neriah, Susana ^{[1
]}

Rogic, Sanja ^{[1
]}

Scott, David W. ^{[1
]}

Tan, King L. ^{[1
]}

Steidl, Christian ^{[1
]}

Sehn, Laurie H. ^{[1
]}

Chan, Wing C. ^{[3
]}

Iqbal, Javeed ^{[3
]}

Meyer, Paul N. ^{[3
]}

Lenz, Georg ^{[4
]}

Wright, George ^{[8
]}

Rimsza, Lisa M. ^{[9
]}

Valentino, Carlo ^{[9
]}

Brunhoeber, Patrick ^{[9
]}

Grogan, Thomas M. ^{[9
]}

Braziel, Rita M. ^{[10
]}

Cook, James R. ^{[12
]}

Tubbs, Raymond R. ^{[12
]}

Weisenburger, Dennis D. ^{[3
]}

Campo, Elias ^{[11
]}

Rosenwald, Andreas ^{[5
]}

Ott, German ^{[5
,6
,7
]}

Delabie, Jan ^{[13
]}

Holcroft, Christina ^{[2
]}

Jaffe, Elaine S. ^{[8
]}

Staudt, Louis M. ^{[8
]}

Gascoyne, Randy D. ^{[1
]}

机构：

[1] British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada

[2] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada

[3] Univ Nebraska Med Ctr, Omaha, NE USA

[4] Charite, D-13353 Berlin, Germany

[5] Univ Wurzburg, Wurzburg, Germany

[6] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[7] Robert Bosch Krankenhaus, Stuttgart, Germany

[8] NCI, NIH, Bethesda, MD 20892 USA

[9] Univ Arizona, Tucson, AZ USA

[10] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[11] Hosp Clin Barcelona, Barcelona, Spain

[12] Cleveland Clin, Cleveland, OH 44106 USA

[13] Radiumhospitalet, Oslo, Norway

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 28期

基金：

加拿大健康研究院;

关键词：

C-MYC; PROGNOSTIC-SIGNIFICANCE; BURKITT-LYMPHOMA; ELDERLY-PATIENTS; R-CHOP; SURVIVAL; BIOMARKER; PREDICTS; DISTINCT; AGE;

D O I：

10.1200/JCO.2011.41.0985

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose 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. Patients and Methods 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. Results 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. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis. J Clin Oncol 30:3452-3459. (C) 2012 by American Society of Clinical Oncology

引用

页码：3452 / 3459

页数：8

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