18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair

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 Marie Vose, Malik E. Juweid

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 repairrelated 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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalEJNMMI Research
Volume4
Issue number1
DOIs
StatePublished - Jan 23 2014

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Follicular Lymphoma
DNA Repair
Lymphoma, Large B-Cell, Diffuse
DNA Replication
Proliferating Cell Nuclear Antigen
Cell Proliferation
Cytostatic Agents
B-Cell Chronic Lymphocytic Leukemia
Genetic Markers
Lymphoma
B-Lymphocytes
Lymph Nodes

Keywords

  • 18 F-fluorothymidine uptake
  • DNA repair
  • Follicular lymphoma
  • Non-hodgkin's lymphoma
  • Positron emission tomography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Wondergem, M. J., Herrmann, K., Syrbu, S., Zijlstra, J. M., Hoetjes, N., Hoekstra, O. S., ... Juweid, M. E. (2014). 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair. EJNMMI Research, 4(1), 1-7. https://doi.org/10.1186/2191-219X-4-3

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 A G M; Moesbergen, Laura M.; Buck, Andreas K.; Vose, Julie Marie; Juweid, Malik E.

In: EJNMMI Research, Vol. 4, No. 1, 23.01.2014, p. 1-7.

Research output: Contribution to journalArticle

Wondergem, MJ, Herrmann, K, Syrbu, S, Zijlstra, JM, Hoetjes, N, Hoekstra, OS, Cillessen, SAGM, Moesbergen, LM, Buck, AK, Vose, JM & Juweid, ME 2014, '18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair', EJNMMI Research, vol. 4, no. 1, pp. 1-7. https://doi.org/10.1186/2191-219X-4-3
Wondergem MJ, Herrmann K, Syrbu S, Zijlstra JM, Hoetjes N, Hoekstra OS et al. 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair. EJNMMI Research. 2014 Jan 23;4(1):1-7. https://doi.org/10.1186/2191-219X-4-3
Wondergem, Marielle J. ; Herrmann, Ken ; Syrbu, Sergei ; Zijlstra, Josée M. ; Hoetjes, Nikie ; Hoekstra, Otto S. ; Cillessen, Saskia A G M ; Moesbergen, Laura M. ; Buck, Andreas K. ; Vose, Julie Marie ; Juweid, Malik E. / 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair. In: EJNMMI Research. 2014 ; Vol. 4, No. 1. pp. 1-7.
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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 repairrelated 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.",
keywords = "18 F-fluorothymidine uptake, DNA repair, Follicular lymphoma, Non-hodgkin's lymphoma, Positron emission tomography",
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T1 - 18 F-fluorothymidine uptake in follicular lymphoma and error-prone DNA repair

AU - Wondergem, Marielle J.

AU - Herrmann, Ken

AU - Syrbu, Sergei

AU - Zijlstra, Josée M.

AU - Hoetjes, Nikie

AU - Hoekstra, Otto S.

AU - Cillessen, Saskia A G M

AU - Moesbergen, Laura M.

AU - Buck, Andreas K.

AU - Vose, Julie Marie

AU - Juweid, Malik E.

PY - 2014/1/23

Y1 - 2014/1/23

N2 - 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 repairrelated 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.

AB - 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 repairrelated 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.

KW - 18 F-fluorothymidine uptake

KW - DNA repair

KW - Follicular lymphoma

KW - Non-hodgkin's lymphoma

KW - Positron emission tomography

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