Usefulness of pyruvate dehydrogenase-E1α expression to determine SUVmax cut-off value of [18F]FDG-PET for predicting lymph node metastasis in lung cancer

Abstract

A more accurate cut-off value of maximum standardized uptake value (SUVmax) in [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG-PET/CT) is necessary to improve preoperative nodal staging in patients with lung cancer. Overall, 223 patients with lung cancer who had undergone [¹⁸F]FDG-PET/CT within 2 months before surgery were enrolled. The expression of glucose transporter-1, pyruvate kinase-M2, pyruvate dehydrogenase-E1α (PDH-E1α), and carbonic anhydrase-9 was evaluated by immunohistochemistry. Clinicopathological background was retrospectively investigated. According to PDH-E1α expression in primary lesion, a significant difference (p = 0.021) in SUVmax of metastatic lymph nodes (3.0 with PDH-positive vs 4.5 with PDH-negative) was found, but not of other enzymes. When the cut-off value of SUVmax was set to 2.5, the sensitivity and specificity were 0.529 and 0.562, respectively, and the positive and negative predictive values were 0.505 and 0.586, respectively. However, when the cut-off value of SUVmax was set according to PDH-E1α expression (2.7 with PDH-positive and 3.2 with PDH-negative), the sensitivity and specificity were 0.441 and 0.868, respectively, and the positive and negative predictive values were 0.738 and 0.648, respectively. The SUVmax cut-off value for metastatic lymph nodes depends on PDH-E1α expression in primary lung cancer. The new SUVmax cut-off value according to PDH-E1α expression showed higher specificity for [¹⁸F]FDG-PET in the diagnosis of lymph node metastasis.

Figure 1

Immunostaining of PDH-E1α, CA9, GLUT1, and PKM2. The immunoreactivity of GLUT1, PKM2, PDH-E1α, and CA9 was evaluated according to the intensity staining of the cell membrane or cytoplasm of cancer cells. Immunostaining intensity score: 0, negative; 1+, weakly positive; 2+, positive; and 3+, strongly positive. Bar, 50 μm. PDH-E1α, pyruvate dehydrogenase E1α; CA9, carbonic anhydrase 9; GLUT1, glucose transporter-1, PKM2; pyruvate kinase-M2.

Figure 2

SUVmax of the primary lesion and metastatic lymph node according to the expression level of glucose metabolism enzymes. (A) Shows the SUVmax of primary tumors in 102 patients with lymph node (LN) metastasis. In contrast, there was no significant difference in the SUVmax of primary tumors according to the expression of glucose metabolism enzymes. (B) Shows the SUVmax of metastatic lymph nodes in all 102 patients. There is a significant difference in the SUVmax of metastatic lymph nodes according to the PDH-E1α expression, but not in GLUT1, CA9, and PKM2 expression. SUV, standard uptake value; PDH-E1α, pyruvate dehydrogenase E1α; CA9, carbonic anhydrase 9; GLUT1, glucose transporter-1, PKM2; pyruvate kinase-M2.

Figure 3

ROC curve of SUVmax according to PDH-E1α expression. In patients with PDH-E1α-positive primary tumors, the optimum cut-off value of SUVmax was 2.7 and AUC was 0.573. In contrast, in patients with PDH-E1α-negative expression tumors, the optimum cut-off value of SUVmax was 3.2 and AUC was 0.613. SUV, standard uptake value; PDH-E1α, pyruvate dehydrogenase E1α; ROC, receiver operating characteristic; AUC, area under the curve.