18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
Please always quote using this URN: urn:nbn:de:bvb:20-opus-121233
- 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 lymphBACKGROUND: 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.…
Author: | Marielle J. Wondergem, Ken Herrmann, Sergei Syrbu, Josée M. Zijlstra, Nikie Hoetjes, Otto S. Hoekstra, Saskia A. G. M. Cillessen, Laura M. Moesbergen, Andreas K. Buck, Julie M. Vose, Malik E. Juweid |
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URN: | urn:nbn:de:bvb:20-opus-121233 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin |
Language: | English |
Parent Title (English): | EJNMMI Research |
Year of Completion: | 2014 |
Volume: | 4 |
Pagenumber: | 3 |
Source: | EJNMMI Research 2014, 4:3. doi:10.1186/2191-219X-4-3 |
DOI: | https://doi.org/10.1186/2191-219x-4-3 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/24397937 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | 18-F-fluorothymidine uptake; DNA repair; follicular lymphoma; non-Hodgkin's lymphoma; positron emission tomography |
Release Date: | 2016/02/17 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |