Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography

Reinhard Bos, Jacobus J M Van der Hoeven, Elsken Van der Wall, Petra Van der Groep, Paul J. Van Diest, Emile F I Comans, Urvi Joshi, Gregg L Semenza, Otto S. Hoekstra, Adriaan A. Lammertsma, Carla F M Molthoff

Research output: Contribution to journalArticle

Abstract

Purpose: Variable uptake of the glucose analog 18fluoradeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared 18FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. Patients and Methods: Preoperative 18FDG-PET scans were performed in 55 patients. 18FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor a(VEGF165); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. Results: There were positive correlations between 18FDG uptake and Glut-1 expression (P <.001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF165, HK II, HK III, and macrophages showed no univariate correlation with 18FDG. In logistic regression, however, HIF-I α and HK II added value to MAI and Glut- 1. Conclusion: 18FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of 18FDG into the cell, HK for entering 18FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1 α for upregulating Glut-1. Together, these features explain why breast cancers vary in 18FDG uptake and elucidate the low uptake in lobular breast cancer.

Original languageEnglish (US)
Pages (from-to)379-387
Number of pages9
JournalJournal of Clinical Oncology
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2002

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Fluorodeoxyglucose F18
Positron-Emission Tomography
Hexokinase
Breast Neoplasms
Facilitative Glucose Transport Proteins
Hypoxia-Inducible Factor 1
Mitotic Index
Lymphocyte Count
Microvessels
Tumor Burden
Cell Size
Necrosis
Macrophages
Glycolysis
Vascular Endothelial Growth Factor A
Neoplasms
Biomarkers
Logistic Models
Immunohistochemistry
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bos, R., Van der Hoeven, J. J. M., Van der Wall, E., Van der Groep, P., Van Diest, P. J., Comans, E. F. I., ... Molthoff, C. F. M. (2002). Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. Journal of Clinical Oncology, 20(2), 379-387. https://doi.org/10.1200/JCO.20.2.379

Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. / Bos, Reinhard; Van der Hoeven, Jacobus J M; Van der Wall, Elsken; Van der Groep, Petra; Van Diest, Paul J.; Comans, Emile F I; Joshi, Urvi; Semenza, Gregg L; Hoekstra, Otto S.; Lammertsma, Adriaan A.; Molthoff, Carla F M.

In: Journal of Clinical Oncology, Vol. 20, No. 2, 15.01.2002, p. 379-387.

Research output: Contribution to journalArticle

Bos, R, Van der Hoeven, JJM, Van der Wall, E, Van der Groep, P, Van Diest, PJ, Comans, EFI, Joshi, U, Semenza, GL, Hoekstra, OS, Lammertsma, AA & Molthoff, CFM 2002, 'Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography', Journal of Clinical Oncology, vol. 20, no. 2, pp. 379-387. https://doi.org/10.1200/JCO.20.2.379
Bos R, Van der Hoeven JJM, Van der Wall E, Van der Groep P, Van Diest PJ, Comans EFI et al. Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. Journal of Clinical Oncology. 2002 Jan 15;20(2):379-387. https://doi.org/10.1200/JCO.20.2.379
Bos, Reinhard ; Van der Hoeven, Jacobus J M ; Van der Wall, Elsken ; Van der Groep, Petra ; Van Diest, Paul J. ; Comans, Emile F I ; Joshi, Urvi ; Semenza, Gregg L ; Hoekstra, Otto S. ; Lammertsma, Adriaan A. ; Molthoff, Carla F M. / Biologic correlates of 18fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 2. pp. 379-387.
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abstract = "Purpose: Variable uptake of the glucose analog 18fluoradeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared 18FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. Patients and Methods: Preoperative 18FDG-PET scans were performed in 55 patients. 18FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor a(VEGF165); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. Results: There were positive correlations between 18FDG uptake and Glut-1 expression (P <.001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF165, HK II, HK III, and macrophages showed no univariate correlation with 18FDG. In logistic regression, however, HIF-I α and HK II added value to MAI and Glut- 1. Conclusion: 18FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of 18FDG into the cell, HK for entering 18FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1 α for upregulating Glut-1. Together, these features explain why breast cancers vary in 18FDG uptake and elucidate the low uptake in lobular breast cancer.",
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AU - Bos, Reinhard

AU - Van der Hoeven, Jacobus J M

AU - Van der Wall, Elsken

AU - Van der Groep, Petra

AU - Van Diest, Paul J.

AU - Comans, Emile F I

AU - Joshi, Urvi

AU - Semenza, Gregg L

AU - Hoekstra, Otto S.

AU - Lammertsma, Adriaan A.

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N2 - Purpose: Variable uptake of the glucose analog 18fluoradeoxyglucose (FDG) has been noticed in positron emission tomography (PET) studies of breast cancer patients, with low uptake occurring especially in lobular cancer. At present, no satisfactory biologic explanation exists for this phenomenon. This study compared 18FDG uptake in vivo with biomarkers expected to be involved in the underlying biologic mechanisms. Patients and Methods: Preoperative 18FDG-PET scans were performed in 55 patients. 18FDG activity was assessed visually by three observers using a four-point score. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut-1); Hexokinase (HK) I, II, and III; macrophages; hypoxia-inducible factor-1-alfa (HIF-1α); vascular endothelial growth factor a(VEGF165); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. Results: There were positive correlations between 18FDG uptake and Glut-1 expression (P <.001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HK I (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1α, VEGF165, HK II, HK III, and macrophages showed no univariate correlation with 18FDG. In logistic regression, however, HIF-I α and HK II added value to MAI and Glut- 1. Conclusion: 18FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of 18FDG into the cell, HK for entering 18FDG into glycolysis, number of tumor cells/volume, proliferation rate (also reflected in necrosis), number of lymphocytes (not macrophages), and HIF-1 α for upregulating Glut-1. Together, these features explain why breast cancers vary in 18FDG uptake and elucidate the low uptake in lobular breast cancer.

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