421 [18F]FDG uptake and expression of immunohistochemical markers 8 Results Twenty-four patients were included, of which 16 (67%) were female. The mean age was 53.1 ± 14.7 years. The median nodule size was 30 mm (interquartile range 24-45). SUVmax, SUVpeak, and SUVmaxratio were statistically significantly different between the groups (Tables 1 and 2). These differences were significant between TN and FP and between TN and TP groups, but not between FP and TP groups. Unsupervised cluster analysis (Figure 2) indicated fair clustering of nodules in TN, FP, and TP groups based on the IRS of the 11 immunomarkers. Many lesions with a high SUVmax appeared to have a high expression of multiple markers, including FP as well as TP nodules. The expression of multiple markers moderately positively correlated with each other: GLUT1 to GLUT3, GLUT4, HK2, and MCT4; GLUT3 to HK2, MCT4, and Ki-67; HK1 to NIS; HK2 to GLUT4, MCT4, and VEGF; MCT4 to Ki-67 (Figure 3). The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak and SUVmax-ratio (Table 2). For GLUT1, both its cytoplasmic (rs(22)=0.715, p<0.001) and membranous (rs(22)=0.450, p=0.03) expression were related to the SUVmax. For GLUT3, only its cytoplasmic expression was correlated with the SUVmax (rs(22)=0.649, p<0.001). Table 3. Correlations between the IRS and SUV SUVmax SUVpeak SUVmax-ratio IHC stain rs p rs p rs p GLUT1 0.731 <0.001 0.731 <0.001 0.720 <0.001 GLUT3 0.579 0.003 0.556 0.005 0.582 0.003 GLUT4 0.301 0.15 0.315 0.13 0.294 0.16 HK1 0.182 0.40 0.237 0.27 0.096 0.66 HK2 0.695 <0.001 0.681 <0.001 0.707 <0.001 HIF1a 0.102 0.64 0.111 0.61 0.124 0.56 MCT4 0.760 <0.001 0.765 <0.001 0.740 <0.001 CA-IX 0.152 0.48 0.113 0.60 0.166 0.44 VEGF 0.373 0.07 0.393 0.054 0.359 0.09 NIS -0.270 0.20 -0.270 0.20 -0.262 0.22 Ki-67 0.319 0.13 0.275 0.19 0.354 0.09 CA-IX, carbonic anhydrase IX. GLUT, glucose transporter. HIF1a, Hypoxia-inducible factor-1 alpha. HK, hexokinase. IRS, immunoreactive score. MCT4, Monocarboxylate transporter 4. NIS, sodium-iodide symporter. rs: Spearman’s rank correlation coefficient (df=22). SUV, standardized uptake value. VEGF, vascular endothelial growth factor.
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