title: Independent prognostic impact of tumour-infiltrating macrophages in early-stage Hodgkin's lymphoma.
abstract: Although patients with early-stage Hodgkin's lymphoma have a high rate of cure, a portion of these are resistant to or relapse after standard treatment. Current prognostic criteria based on clinical and laboratory parameters at diagnosis do not allow to accurately identify the subset of patients with less favourable clinical outcome. An increased number of tumour-infiltrating macrophages was found to be associated with shortened survival in patients with classic Hodgkin's Lymphoma. The aim of this study was to assess the clinical significance of the proportion of CD68-positive infiltrating macrophages in patients with early-stage classic Hodgkin's lymphoma. By using immunohistochemistry technique, we evaluated for CD68 expression diagnostic biopsies of 106 patients affected by supradiaphragmatic early-stage classic Hodgkin's lymphoma treated at our institution since 2000 to 2010. All patients were treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by radiotherapy in the majority. The 2-year overall survival and progression-free survival (PFS) in the entire cohort were 97% and 83% respectively. The 2-year PFS was statistically different between patients with favourable and those with unfavourable prognosis according to the European Organisation for Research and Treatment of Cancer (EORTC) risk criteria (96% vs 79%, p = 0.039) and between patients having less than 25% of CD68-positive infiltrating macrophages and those with more than 25% (85% vs 67%, p = 0.012). All patients with favourable EORTC criteria had CD68 expression lower than 25%. Within those with unfavourable EORTC criteria, patients with a CD68+ count greater than 25% had a worse 2-year PFS than patients having values lower than 25% (64% vs 82%, p = 0.03). Moreover, in multivariate analysis, after adjusting for CD68+ macrophages count and EORTC score, only CD68+ macrophages count higher than 25% retained a prognostic effect on PFS (hazard ratio = 2.8, 95%CI: 1.1-7.6, p = 0.038). Our data show that a proportion of tumour-infiltrating macrophages greater than 25% is associated with unfavourable clinical outcome in patients with early-stage Hodgkin's lymphoma Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gotti
authors.affiliation: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Nicola
authors.affiliation: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fiaccadori
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Ferretti
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sciarra
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Costanza
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bono
authors.affiliation: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Molo
authors.affiliation: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Maffi
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Giorgio A
authors.initials: GA
authors.lastname: Croci
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Varettoni
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Frigeni
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bonfichi
authors.affiliation: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.affiliation: Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D001706:Biopsy; D002452:Cell Count; D005260:Female; D006689:Hodgkin Disease / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: EORTC criteria; Hodgkin's lymphoma; tumour-infiltrating macrophages