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FDG-PET SUVmax Correlates with Increased Expression of Glut1, p53, EGFR, and Ki67 in Patients with Non-Small Cell Lung Cancer
M. D. Taylor, P. W. Smith, W. K. Brix, M. R. Wick, N. Theodosakis, B. Swenson, B. J. Kozower, C. L. Lau, D. R. Jones. University of Virginia, Charlottesville, VA,
BACKGROUND:
The best current non-invasive surrogate for tumor biology is FDG-PET. Both FDG-PET SUVmax and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in non-small cell lung cancer (NSCLC). Interestingly, there is no data which examines the relationship between FDG-PET SUVmax and expression of these tumors markers in NSCLC. The purpose of this study was to determine the correlation of tumor markers with FDG-PET SUVmax in NSCLC.
METHODS:
FDG-PET SUVmax was calculated in patients with NSCLC (N=149) of which 68 (65%) had adenocarcinoma. No patient had induction chemoradiotherapy. Intraoperative NSCLC tissue was obtained and tissue microarrays were created. IHC analysis was performed for 6 known NSCLC tumor markers (GLUT1, p53, cyclin D1, EGFR, Ki67, and VEGF). Assessment of each tumor marker was made by an independent, blinded pathologist using common grading criteria of intensity and percentage of cells stained. The product of each tumor marker was calculated by multiplying intensity by percentage of cells stained. Subgroup analysis based on nodal status was performed. A p-value ≤ 0.05 was considered statistically significant.
RESULTS:
There were 79 men (53%) and 70 women (47%) with a mean age of 68±9 years. Pathologic staging included stage I (N=93, 62%), stage II (N=35, 23%), stage III disease (N=20, 13%), and stage IV disease (N=1, 0.7%). PET SUVmax correlated with T stage (p=0.005), N-stage (p=0.07), and greatest tumor dimension (p=0.0001). In addition, increasing SUVmax values correlated with increased expression of Ki67 (p=0.006), GLUT1 transporter (p=0.0001), p53 (p=0.04), and EGFR (p=0.008). Pathologic N1 or N2 disease was present in 45 (30%) patients. Tumor SUVmax was significantly higher in node-positive patients compared to node-negative patients (8.5±0.6 vs. 6.4±0.5, p=0.005). Subgroup analysis revealed that node-positive patients had increased Ki67 expression (47±4.5% vs. 33±2.8%, p=0.01) and GLUT1 transporter expression (47±4% vs. 34±3%, p=0.01). Table 1 illustrates that as the SUVmax increases there is a concomitant and significant increase in tumor Ki67, Glut1, EGFR, and p53 expression levels.
CONCLUSIONS:
FDG-PET SUVmax correlates with an increased expression of Ki67, GLUT1 transporter, EGFR, and p53. In addition, expression of these markers in NSCLC increased with increasing SUVmax values. This study provides the first evidence that FDG-PET SUVmax correlates with expression of key oncoproteins involved in NSCLC promotion, proliferation, and metabolic activity.
Table 1-FDG-PET SUVmax and Tumor Markers (Mean)| SUVmax | Ki67 (%) | GLUT1 intensity | EGFR (%) | p53 product(%) | 0-2.5
(n=25) | 27±6 | 1.1±0.3 | 10±4 | 64±19 | 2.6-5.0
(n=37) | 37±5 | 1.7±0.2 | 27±6 | 77±14 | 5.1-10
(n=53) | 37±4 | 2.0±0.1 | 34±5 | 93±13 | >10
(n=34) | 47±5 | 2.5±0.2 | 37±7 | 104±19 |
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