title: The prognostic impact of tumour-associated macrophages and Reed-Sternberg cells in paediatric Hodgkin lymphoma.
abstract: BACKGROUND
  Tumour-associated macrophages (TAM) are associated with treatment failure in adults with Hodgkin lymphoma (HL). Equivalent data in paediatric HL are sparse. We aimed to determine the prognostic significance of TAM and Reed-Sternberg (RS) cells in paediatric HL.
  
  
  METHODS
  All children aged 0-18 with HL between 1980 and 2009 with available diagnostic biopsy material were identified. A treatment failure-enriched cohort was assembled. Demographic, disease and outcome data were abstracted. Tissue microarrays with duplicate cores were constructed from diagnostic biopsy material and stained with immunohistochemical markers for TAM (CD68, CD163) and RS (CD30). A high score was defined as >5% positive cells relative to overall cellularity in any core. The association of candidate variables with event-free survival (EFS) was determined using Cox proportional hazards.
  
  
  RESULTS
  The final study cohort comprised 96 patients with a median age of 14 years (interquartile range 11-15). Agreement on scores between cores from the same biopsy revealed weighted kappas of 0.60, 0.68 and 0.73 for CD30, CD68 and CD163 respectively, indicating moderate tumour heterogeneity. In univariate analysis, a high CD30 score was significantly associated with treatment failure (hazard ratio (HR) 2.27; 95th confidence interval 1.01-5.11; p<0.05). High CD68 and CD163 scores were not associated with EFS.
  
  
  CONCLUSIONS
  Unlike adult HL, a higher percentage of RS cells was associated with poor outcome, while a higher percentage of TAM was not. Adult HL findings may not extend to paediatric HL. Cooperative group trials of paediatric HL should prospectively determine the association of different components of the tumour microenvironment with outcome.
authors.affiliation: Division of Hematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Electronic address: sumit.gupta@sickkids.ca.
authors.forename: Sumit
authors.initials: S
authors.lastname: Gupta
authors.forename: Stacy
authors.initials: S
authors.lastname: Yeh
authors.forename: Rose
authors.initials: R
authors.lastname: Chami
authors.forename: Angela
authors.initials: A
authors.lastname: Punnett
authors.forename: Catherine
authors.initials: C
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008264:Macrophages / Q000276:immunology* / Q000473:pathology*; D008297:Male; D011379:Prognosis; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000473:pathology*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
keywords: Child; Hodgkin lymphoma; Macrophages; Prognosis; Reed-Sternberg cells