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

被引:465
作者
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
机构
[1] Vrije Univ Amsterdam, Ctr Med, Positron Emiss Tomog Res Ctr, Dept Nucl Med, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Ctr Med, Positron Emiss Tomog Res Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Ctr Med, Positron Emiss Tomog Res Ctr, Dept Med Oncol, NL-1007 MB Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Ctr Med, Positron Emiss Tomog Res Ctr, Dept Nucl Med, NL-1007 MB Amsterdam, Netherlands
[5] Amstelveen Hosp, Dept Internal Med, Amstelveen, Netherlands
[6] Johns Hopkins Univ, Sch Med, Inst Med Genet, Dept Pediat & Med, Baltimore, MD USA
关键词
D O I
10.1200/JCO.20.2.379
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Variable uptake of the glucose analog (18)fluorodeoxyglucose (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 (18)FDG uptake in vivo with biomarkers expected: to be involved in the underlying biologic mechanisms. Patients and Methods: Preoperative (18)FDG-PET scans were performed in 55 patients. (18)FDG 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-1alpha); vascular endothelial growth factor (VEGF(165)); and microvessels. Mitotic activity index (MAI), amount of necrosis, number of lymphocytes, and tumor cells/volume were assessed. Results: There were positive correlations between (18)FDG uptake and Glut-1 expression (P < .001), MAI (P = .001), amount of necrosis (P = .010), number of tumor cells/volume (P = .009), expression of HKI (P = .019), number of lymphocytes (P = .032), and microvessel density (r = .373; P = .005). HIF-1alpha, VEGF(165), HK II, HK III, and macrophages showed no univariate correlation with (18)FDG. In logistic regression, however, HIF-1alpha and HK II added value to MAI and Glut-1. Conclusion: (18)FDG uptake in breast cancer is a function of microvasculature for delivering nutrients, Glut-1 for transportation of (18)FDG 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-1alpha for up-regulating Glut-1. Together, these features explain why breast cancers vary in (18)FDG uptake and elucidate the low uptake in lobular breast cancer. (C) 2002 by American Society of Clinical Oncology.
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页码:379 / 387
页数:9
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