[18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and inflammatory lesions of the lung

Abstract

Purpose: The aim of this study was to evaluate the relationships among [18F]fluorodeoxyglucose ([18F]-FDG) uptake, Glut-1 and HK-II expressions, and grade of inflammation in resected lung lesions.

Materials and methods: Sixty patients had undergone preoperative 18F-FDG-PET imaging and thoracotomy. For semiquantitative analysis of 18F-FDG uptake, partial volume effect corrected maximum standardized uptake values (pSUVs) were calculated. Immunohistochemical staining was performed in resected specimens using anti-Glut-1, anti-HK-II, and anti-proliferative cellular nuclear antigen (PCNA) antibodies, and immunoreactivities were scored as G-, H-, and P-indexes on a five-point scale (0: 0%; 1: 20%, 2: 40%; 3: 60%; 4: 80%, and 5: 100% percentages of strongly immunoreactive cells).Grade of inflammation was also evaluated.

Results: The malignant lesions had higher pSUV and higher G- and H- than nonmalignant lesions. pSUVs correlated with the G- (p < .001), H- (p < .01), and P-indexes (p < .01) in malignant lesions. In adenocarcinomas, cancers with lower differentiation showed higher expression of Glut-1 and HK-II than those with higher differentiation. A positive linear regression was observed between pSUVs and the grading of inflammation in nonmalignant lesions (p < .05).

Conclusions: Our study indicates that 18F-FDG uptake in lung cancer correlates well with the Glut-1, HK-II, and PCNA expression. For nonmalignant lesions, the presence of a higher inflammatory process correlated with 18F-FDG uptake.

Figure 1

pSUV values plotted with respect to tumor histologic diagnosis. (A) The pSUVs were higher for malignant lesions (mean ± SD, 10.9 ± 7.3) than that for nonmalignant lesions (8.0 ± 6.3) (NS). (B) The SCC showed the highest pSUV (mean ± SD, 19.5 ± 7.50) (ANOVA, P < 0.01). The AC lesions had higher pSUVs than that for nonmalignant lesions (NS). AC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung.

Figure 2

Immunohistochemical findings and [¹⁸F]FDG-PET examinations from selected patients enrolled in the present study. (A, D, and G) Glut-1 expression, HK-II expression, and [¹⁸F]FDG-PET examination from the same patient (patient 33) with well-differentiated SCC, respectively. The highest expression of Glut-1 was observed in the membranes of cancer cells (grade 5) (original magnification, x 10), whereas the expression of HK-II was observed throughout the cytoplasm as small punctuate areas (grade 4) (original magnification, x 10). The [¹⁸F]FDG-PET examination showed a high [¹⁸F]FDG uptake in the posterior lower lobe of the right lung (panel G; arrow) on the transaxial slice (pSUV = 14.1). (B, E, and H) Glut-1 expression and two representative [¹⁸F]FDG-PET reconstructed slices (coronal and transaxial slices, respectively) from a patient (patient 21) with AC (papillary type, moderate differentiated), respectively. The expression of Glut-1 can be observed in the membranes of cancer cells and as granules throughout the cell cytoplasm (grade 5) (original magnification, x 10). The [¹⁸F]FDG PET examination showed a high uptake in the left lung (panel H; arrow) (pSUV = 12.4). (C, F, and I) Glut-1 expression, HK-II expression, and [¹⁸F]FDG PET examination from a patient with pulmonary tuberculosis (patient 48), respectively. The expression of Glut-1 can be observed in the membranes of cells in the center of the pulmonary granuloma (grade 2) (original magnification, x4), whereas the expression of HK-II can be observed in areas surround caseating granulomas throughout the cytoplasm (grade 3) (original magnification, x4). The [¹⁸F]FDG-PET examination showed a moderate [¹⁸F]FDG uptake in the upper lobe of the left lung (panel I; arrow) on the transaxial slice (pSUV = 6.9).

Figure 3

Comparative analyses between grades of Glut-1 (G-index), HK-II (H-index), or PCNA (P-index) expressions with pSUV values in pulmonary malignant lesions. (A) The G-index showed a significant positive relationship with pSUV (r = 0.66, P < .001). (B) The H-index showed a significant positive relationship with pSUV (r = 0.43, P < .01). (C) The P-index showed a significant positive relationship with pSUV (r = 042, P < .01).

Figure 4

Immunohistochemical findings from a selected patient (patient 20). In the present study, the HK-II expression in smooth muscle cells was often observed (arrow).

Figure 5

A comparative analyses between grades of Glut-1 (G-index) or HK-II (H-index) expressions, with grade of PCNA (P-index) expressions in pulmonary malignant lesions. (A) The G-index and P-index showed a significant positive relationship (r = 0.58, P < .01). (B) The H-index and P-index showed a significant positive relationship (r = 0.52, P < .01).

Figure 6

Tumor histologic differentiations (well-moderated and poorly differentiated) plotted with respect to the grade of Glut-1 (G-index) expressions in AC of lung. The poorly differentiated AC of the lung showed the highest grade of anti-Glut-1 antibody expression (ANOVA, P < .001). No staining was observed in specimens from well-differentiated AC. A linear regression was observed between G-index and the grade of differentiation (r² = 0.45, P < .001).

Figure 7

A comparative analysis between pSUV values and grade of inflammatory process in nonmalignant lesions. A linear regression was observed between pSUV and the grade of inflammation (r² = 0.61, P < .05).