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18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895783/ https://www.ncbi.nlm.nih.gov/pubmed/24397937 http://dx.doi.org/10.1186/2191-219X-4-3 |
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author | Wondergem, Marielle J Herrmann, Ken Syrbu, Sergei Zijlstra, Josée M Hoetjes, Nikie Hoekstra, Otto S Cillessen, Saskia AGM Moesbergen, Laura M Buck, Andreas K Vose, Julie M Juweid, Malik E |
author_facet | Wondergem, Marielle J Herrmann, Ken Syrbu, Sergei Zijlstra, Josée M Hoetjes, Nikie Hoekstra, Otto S Cillessen, Saskia AGM Moesbergen, Laura M Buck, Andreas K Vose, Julie M Juweid, Malik E |
author_sort | Wondergem, Marielle J |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3895783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer |
record_format | MEDLINE/PubMed |
spelling | pubmed-38957832014-01-24 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair Wondergem, Marielle J Herrmann, Ken Syrbu, Sergei Zijlstra, Josée M Hoetjes, Nikie Hoekstra, Otto S Cillessen, Saskia AGM Moesbergen, Laura M Buck, Andreas K Vose, Julie M Juweid, Malik E EJNMMI Res Original Research 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. Springer 2014-01-08 /pmc/articles/PMC3895783/ /pubmed/24397937 http://dx.doi.org/10.1186/2191-219X-4-3 Text en Copyright © 2014 Wondergem et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Wondergem, Marielle J Herrmann, Ken Syrbu, Sergei Zijlstra, Josée M Hoetjes, Nikie Hoekstra, Otto S Cillessen, Saskia AGM Moesbergen, Laura M Buck, Andreas K Vose, Julie M Juweid, Malik E 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title | 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title_full | 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title_fullStr | 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title_full_unstemmed | 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title_short | 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair |
title_sort | 18 f-fluorothymidine uptake in follicular lymphoma and error-prone dna repair |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895783/ https://www.ncbi.nlm.nih.gov/pubmed/24397937 http://dx.doi.org/10.1186/2191-219X-4-3 |
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