title: Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL).
abstract: We studied the role of multiple biomarkers in determining outcome in follicular lymphoma (FL), concentrating in particular on the role of benign macrophages. The study group consisted of uniformly staged and treated patients with FL enrolled in a phase 2 trial between 1987 and 1993. All patients were younger than 61 years of age, had advanced-stage FL, and were treated with a multiagent chemotherapy regimen, BP-VACOP (bleomycin, cisplatin, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone), followed by involved region radiation. The median follow-up of living patients was 12.5 years, and the median survival was 16.3 years. The International Prognostic Index (IPI) was predictive of overall survival (OS) (P = .003). Biopsy specimens from all cases were stained with an anti-CD68 antibody. Of the 99 evaluable patients with FL, 87 had less than 15 CD68+ macrophages/high-power field (hpf) (median, 7; range, 1-14) and 12 had more than 15 CD68+ macrophages/hpf (median, 20; range, 16-25) with a median OS of 16.3 vs 5.0 years, respectively (P < .001). A multivariate Cox model that included the IPI score, the histologic grade, and the lymphoma-associated macrophage (LAM) score, showed IPI and LAM to be independent predictors of OS (P = .009 and P = .004, respectively). The LAM content of FL predicts survival, and these data support a prominent role for nonneoplastic immune cells in the biology of FL.
authors.affiliation: Department of Pathology, BC Cancer Agency, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Hamid
authors.initials: H
authors.lastname: Masoudi
authors.forename: Brian F
authors.initials: BF
authors.lastname: Skinnider
authors.forename: Karey
authors.initials: K
authors.lastname: Shumansky
authors.forename: John J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: Karamjit
authors.initials: K
authors.lastname: Gill
authors.forename: Richard
authors.initials: R
authors.lastname: Klasa
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voss
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003131:Combined Modality Therapy; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality*; D008264:Macrophages / Q000166:cytology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; C067980:CD68 antigen, human; D000097382:CD68 Molecule