title: High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy.
abstract: BACKGROUND
  Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy.
  
  
  METHODS
  One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data.
  
  
  RESULTS
  Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)].
  
  
  CONCLUSIONS
  These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.
authors.affiliation: Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Cardesa-Salzmann
authors.forename: Luis
authors.initials: L
authors.lastname: Colomo
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gutierrez
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Dennis
authors.initials: D
authors.lastname: Weisenburger
authors.forename: Fina
authors.initials: F
authors.lastname: Climent
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.forename: Santiago
authors.initials: S
authors.lastname: Mercadal
authors.forename: Leonor
authors.initials: L
authors.lastname: Arenillas
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.forename: Ray
authors.initials: R
authors.lastname: Tubbs
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Jose L
authors.initials: JL
authors.lastname: Mate
authors.forename: Lisa
authors.initials: L
authors.lastname: Rimsza
authors.forename: Rita
authors.initials: R
authors.lastname: Braziel
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Louis
authors.initials: L
authors.lastname: Staudt
authors.forename: Pedro
authors.initials: P
authors.lastname: Jares
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D015203:Reproducibility of Results; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000069283:Rituximab