title: 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair.
abstract: BACKGROUND
  We observed a disproportional 18 F-fluorothymidine (F-FLT) uptake in follicular lymphoma (FL) relative to its low cell proliferation. We tested the hypothesis that the 'excess' uptake of 18 F-FLT in FL is related to error-prone DNA repair and investigated whether this also contributes to 18 F-FLT uptake in diffuse large B cell lymphoma (DLBCL).
  
  
  METHODS
  We performed immunohistochemical stainings to assess the pure DNA replication marker MIB-1 as well as markers of both DNA replication and repair like PCNA, TK-1 and RPA1 on lymph node biopsies of 27 FLs and 35 DLBCLs. In 7 FL and 15 DLBCL patients, 18 F-FLT-PET had been performed.
  
  
  RESULTS
  18 F-FLT uptake was lower in FL than in DLBCL (median SUVmax 5.7 vs. 8.9, p = 0,004), but the ratio of 18 F-FLT-SUVmax to percentage of MIB-1 positive cells was significantly higher in FL compared with DLBCL (p = 0.001). The median percentage of MIB-1 positive cells was 10% (range, 10% to 20%) in FL and 70% (40% to 80%) in DLBCL. In contrast, the median percentages of PCNA, TK-1 and RPA1 positive cells were 90% (range, 80 to 100), 90% (80 to 100) and 100% (80 to 100) in FL versus 90% (60 to 100), 90% (60 to 100) and 100% (80 to 100) in DLBCL, respectively.
  
  
  CONCLUSIONS
  This is the first demonstration of a striking discordance between 18 F-FLT uptake in FL and tumour cell proliferation. High expression of DNA replication and repair markers compared with the pure proliferation marker MIB-1 in FL suggests that this discordance might be due to error-prone DNA repair. While DNA repair-related 18 F-FLT uptake considerably contributes to 18 F-FLT uptake in FL, its contribution to 18 F-FLT uptake in highly proliferative DLBCL is small. This apparently high contribution of DNA repair to the 18 F-FLT signal in FL may hamper studies where 18 F-FLT is used to assess response to cytostatic therapy or to distinguish between FL and transformed lymphoma.
authors.affiliation: Department of Haematology, VU University Medical Center (VUMC), De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands. m.wondergem@vumc.nl.
authors.forename: Marielle J
authors.initials: MJ
authors.lastname: Wondergem
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.forename: Sergei
authors.initials: S
authors.lastname: Syrbu
authors.forename: Josée M
authors.initials: JM
authors.lastname: Zijlstra
authors.forename: Nikie
authors.initials: N
authors.lastname: Hoetjes
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: Saskia Agm
authors.initials: SA
authors.lastname: Cillessen
authors.forename: Laura M
authors.initials: LM
authors.lastname: Moesbergen
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Malik E
authors.initials: ME
authors.lastname: Juweid