title: The prognostic significance of the intra-follicular tumor cell proliferative rate in follicular lymphoma.
abstract: OBJECTIVE
  In follicular lymphoma histological grading is used to predict clinical behavior and to stratify patients for treatment. However, the reproducibility of histological grading is poor and the clinical significance of the difference between grade 1 and grade 2 follicular lymphoma is unclear. Data on proliferation characteristics with respect to prognosis in follicular lymphoma are inconsistent.
  
  
  METHODS
  We assessed the Proliferation Index in follicles, using Mib-1 immunohistochemical staining in lymph node biopsies from 51 patients with follicular lymphoma who were receiving uniform first-line treatment consisting of cyclophosphamide, vincristine, prednisone and interferon alpha2b.
  
  
  RESULTS
  The median Proliferation Index was 16.9 (range 3.1-49.2). In grades 1 and 2 follicular lymphoma (n=45) it was 16.1, compared to 24.2 in grade 3 (n=6; p=0.02). At a median follow-up of 71 months, patients with a Proliferation Index below the median had a significantly prolonged time to progression (median not reached vs. 15 months for those with a Proliferation Index above the median; p=0.0006) and improved overall survival (median not reached vs. 42 months, respectively; p=0.002). In multivariate analysis, the Proliferation Index retained its predictive value. Additional prognostic information was especially provided in patients with a low International Prognostic Index. Histological grade did not predict outcome.
  
  
  CONCLUSIONS
  The Proliferation Index is a biological marker that is strongly and independently predictive for outcome in follicular lymphoma, as shown even in this relatively small series of patients. It is easily applicable and reproducible and therefore superior to histological grading in identifying clinically aggressive follicular lymphoma, requiring other types of treatment.
authors.affiliation: Department of Haematology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Ad
authors.initials: A
authors.lastname: Koster
authors.forename: Hedwig A
authors.initials: HA
authors.lastname: Tromp
authors.forename: John M M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: George F
authors.initials: GF
authors.lastname: Borm
authors.forename: Konnie
authors.initials: K
authors.lastname: Hebeda
authors.forename: Marius A
authors.initials: MA
authors.lastname: Mackenzie
authors.forename: Joannes H J M
authors.initials: JH
authors.lastname: van Krieken
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001706:Biopsy; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen