title: The expression of the peripheral cannabinoid receptor CB2 has no effect on clinical outcome in diffuse large B-cell lymphomas.
abstract: BACKGROUND
  The peripheral cannabinoid receptor (CB2) is mainly detected on B cells in the germinal centers (GCs) of the immune system, using an antibody directed against the extra cellular N-terminal domain of the receptor. We retrospectively investigated the CB2 receptor expression in diffuse large B-cell lymphomas (DLBCL) and its clinical relevance for treatment outcome.
  
  
  METHODS
  We have constructed a tissue micro-array (TMA) using lymphoma tissue of a large cohort of patients with DLBCL (N = 104) who were treated with CHOP.
  
  
  RESULTS
  Forty-five out of 79 evaluable cases (57%) were CB2 positive. The expression of CB2 receptors was variably present in both the germinal center B cell (GCB) (n = 31) and the non-GCB/activated B-cell (ABC) (n = 43) DLBCL subtypes. CB2 positivity was not associated with a different outcome in this patient cohort (CR; P = 0.87, EFS; P = 0.32, DFS; P = 0.06 and OS; P = 0.18). Implementation of CB2 expression in the Hans algorithm using the markers CD10, BCL6, and MUM1 did not result in added prognostic value (all P-values >0.1).
  
  
  CONCLUSIONS
  We hypothesize that although CB2 is normally expressed in GCs, the expression in one of the malignant counterparts such as DLBCL is aberrant. This may be an explanation for the absence of prognostic relevance for the expression of this protein.
authors: Departments of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands. n.rayman@erasmusmc.nl
authors: Nazik
authors: N
authors: Rayman
authors: King H
authors: KH
authors: Lam
authors: Bronno
authors: B
authors: van der Holt
authors: Clara
authors: C
authors: Koss
authors: Joost
authors: J
authors: van Leeuwen
authors: Leo M
authors: LM
authors: Budel
authors: Andries H
authors: AH
authors: Mulder
authors: Pieter
authors: P
authors: Sonneveld
authors: Ruud
authors: R
authors: Delwel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D018858:Germinal Center / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D051560:Proto-Oncogene Proteins c-bcl-6; D043885:Receptor, Cannabinoid, CB2; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human