Journal article
18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
EJNMMI research, Vol.4(1), pp.3-3
12/2014
DOI: 10.1186/2191-219X-4-3
PMCID: PMC3895783
PMID: 24397937
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.
Details
- Title: Subtitle
- 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
- Creators
- Marielle J Wondergem - Amsterdam UMC Location Vrije Universiteit AmsterdamKen Herrmann - Technische Universität MünchenSergei Syrbu - University of IowaJosée M Zijlstra - Amsterdam UMC Location Vrije Universiteit AmsterdamNikie Hoetjes - Amsterdam UMC Location Vrije Universiteit AmsterdamOtto S Hoekstra - Amsterdam UMC Location Vrije Universiteit AmsterdamSaskia AGM Cillessen - Amsterdam UMC Location Vrije Universiteit AmsterdamLaura M Moesbergen - Amsterdam UMC Location Vrije Universiteit AmsterdamAndreas K Buck - Technische Universität MünchenJulie M Vose - Nebraska Medical CenterMalik E Juweid - University of Jordan
- Resource Type
- Journal article
- Publication Details
- EJNMMI research, Vol.4(1), pp.3-3
- DOI
- 10.1186/2191-219X-4-3
- PMID
- 24397937
- PMCID
- PMC3895783
- NLM abbreviation
- EJNMMI Res
- ISSN
- 2191-219X
- eISSN
- 2191-219X
- Publisher
- Springer
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984186406802771
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