title: Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Graham W
authors.initials: GW
authors.lastname: Slack
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Savage
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Susana
authors.initials: S
authors.lastname: Ben-Neriah
authors.forename: Sanja
authors.initials: S
authors.lastname: Rogic
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: King L
authors.initials: KL
authors.lastname: Tan
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Paul N
authors.initials: PN
authors.lastname: Meyer
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Carlo
authors.initials: C
authors.lastname: Valentino
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunhoeber
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: James R
authors.initials: JR
authors.lastname: Cook
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Christina
authors.initials: C
authors.lastname: Holcroft
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000069283:Rituximab; D015996:Survival Rate; D014178:Translocation, Genetic; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone