title: The Prognostic Impact of CD163-Positive Macrophages in Follicular Lymphoma: A Study from the BC Cancer Agency and the Lymphoma Study Association.
abstract: OBJECTIVE
  We aimed to assess the prognostic significance of follicular lymphoma-associated macrophages in the era of rituximab treatment and maintenance.
  
  
  METHODS
  We applied immunohistochemistry for CD68 and CD163 to two large tissue microarrays (TMA). The first TMA included samples from 186 patients from the BC Cancer Agency (BCCA) who had been treated with first-line systemic treatment including rituximab, cyclophosphamide, vincristine, and prednisone. The second contained 395 samples from PRIMA trial patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and randomized to rituximab maintenance or observation. Macrophage infiltration was assessed using Aperio image analysis. Each of the two cohorts was randomly split into training/validation sets.
  
  
  RESULTS
  An increased CD163-positive pixel count was predictive of adverse outcome in the BCCA dataset [5-year progression-free survival (PFS) 38% vs. 72%, respectively, P = 0.004 in the training cohort and 5-year PFS 29% vs. 61%, respectively, P = 0.004 in the validation cohort]. In the PRIMA trial, an increased CD163 pixel count was associated with favorable outcome (5-year PFS 60% vs. 44%, respectively, P = 0.011 in the training cohort and 5-year PFS 55% vs. 37%, respectively, P = 0.030 in the validation cohort).
  
  
  CONCLUSIONS
  CD163-positive macrophages predict outcome in follicular lymphoma, but their prognostic impact is highly dependent on treatment received.
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Robert
authors: R
authors: Kridel
authors: Département de bio-pathologie, Institut Paoli-Calmettes, Marseille, France.
authors: Luc
authors: L
authors: Xerri
authors: Lymphoma Academic Research Organisation, Centre Hospitalier Lyon-Sud, Lyon, France.
authors: Bénédicte
authors: B
authors: Gelas-Dore
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: King
authors: K
authors: Tan
authors: Hematology, University Hospital, Vandoeuvre Les Nancy, France.
authors: Pierre
authors: P
authors: Feugier
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Ayesha
authors: A
authors: Vawda
authors: Pathology, Hôpital Necker, Paris, France.
authors: Danielle
authors: D
authors: Canioni
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Pedro
authors: P
authors: Farinha
authors: Lymphoma Academic Research Organisation, Centre Hospitalier Lyon-Sud, Lyon, France.
authors: Sami
authors: S
authors: Boussetta
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Alden A
authors: AA
authors: Moccia
authors: Hematology, Hopital Saint Louis, Paris, France.
authors: Pauline
authors: P
authors: Brice
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Elizabeth A
authors: EA
authors: Chavez
authors: Medical Biophysics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Alastair H
authors: AH
authors: Kyle
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: David W
authors: DW
authors: Scott
authors: Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Ashley D
authors: AD
authors: Sanders
authors: APHP, Hôpital Saint-Antoine, Paris, France.
authors: Bettina
authors: B
authors: Fabiani
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Graham W
authors: GW
authors: Slack
authors: Medical Biophysics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Andrew I
authors: AI
authors: Minchinton
authors: Lymphoid Malignancies Unit, Hôpital Henri Mondor, Créteil and University Paris Est Créteil, France.
authors: Corinne
authors: C
authors: Haioun
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Joseph M
authors: JM
authors: Connors
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Laurie H
authors: LH
authors: Sehn
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors: Christian
authors: C
authors: Steidl
authors: Centre for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada. gilles.salles@chu-lyon.fr rgascoyn@bccancer.bc.ca.
authors: Randy D
authors: RD
authors: Gascoyne
authors: Hospices Civils de Lyon, Université Claude Bernard, Pierre-Bénite, France. gilles.salles@chu-lyon.fr rgascoyn@bccancer.bc.ca.
authors: Gilles
authors: G
authors: Salles
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D000069283:Rituximab / Q000008:administration & dosage*; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003520:Cyclophosphamide; D004317:Doxorubicin; D011956:Receptors, Cell Surface; D000069283:Rituximab; D014750:Vincristine; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule