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

• Published in: Journal of clinical oncology Vol. 30; no. 28; pp. 3452 - 3459
• Main Authors: JOHNSON, Nathalie A, SLACK, Graham W, 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, SAVAGE, Kerry J, 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, CONNORS, Joseph M, GASCOYNE, Randy D, BEN-NERIAH, Susana, ROGIC, Sanja, SCOTT, David W, TAN, King L, STEIDL, Christian, SEHN, Laurie H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.10.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cyclophosphamide - therapeutic use; Disease-Free Survival; Doxorubicin - therapeutic use; Female; Gene Expression Profiling; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Medical sciences; Middle Aged; ORIGINAL REPORTS; Prednisone - therapeutic use; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-myc - genetics; Rituximab; Survival Rate; Translocation, Genetic; Tumors; Vincristine - therapeutic use; Young Adult; Antineoplastic agent; Concurrent; Monoclonal antibody; Doxorubicin; Alkaloid; Isomerases; Cancerology; Lymphoproliferative syndrome; Immunotherapy; Antimitotic; Protooncogene; Corticosteroid; DNA topoisomerase (ATP-hydrolysing); Enzyme; Enzyme inhibitor; Rituximab; B cell neoplasm; Malignant hemopathy; Prednisone; Topoisomerase II inhibitor; Non Hodgkin lymphoma; Vincristine; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Treatment; Nitrogen mustard; C-Onc gene; Adrenal hormone; myc Gene; Diffuse large B cell lymphoma; Anthracyclins; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.41.0985

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.