Abstract
Glucose metabolism is necessary for tumor progression, metastasis, and survival in various human cancers. Glucose transporter 1 (GLUT1), in particular, plays an important role in the mechanism of ¹⁸F-FDG (2-[¹⁸F]-fluoro-2-deoxy-d-glucose) within tumor cells. However, little is known about the clinicopathological significance of GLUT1 in patients with pulmonary pleomorphic carcinoma (PPC). Adenocarcinoma, squamous cell carcinoma, adenosquamous cell carcinoma, poorly differentiated carcinoma, large cell carcinoma, and others were identified as epithelial components, and spindle-cell type, giant-cell type, and both spindle- and giant-cell types were identified as sarcomatous components. This study was performed to determine the prognostic impact of GLUT1 expression in PPC. Patients with surgically resected PPC (n = 104) were evaluated by immunohistochemistry analysis to detect GLUT1 expression and determine the Ki-67 labeling index using specimens of the resected tumors. GLUT1 was highly expressed in 48% (50/104) of all patients, 42% (20/48) of the patients with an adenocarcinoma component, and 53% (30/56) of the patients with a nonadenocarcinoma component. High expression of GLUT1 was significantly associated with advanced stage, vascular invasion, pleural invasion, and tumor cell proliferation as determined by Ki-67 labeling. GLUT1 expression and tumor cell proliferation were significantly correlated according to the Ki-67 labeling in all patients (Spearman’s rank; r = 0.25, p < 0.01). In multivariate analysis, GLUT1 was identified as a significant independent marker for predicting a poor prognosis. GLUT1 is an independent prognostic factor for predicting the poor prognosis of patients with surgically resected PPC.
Highlights
Pulmonary pleomorphic carcinoma (PPC) is a rare disease with an incidence of 0.1%–0.4% among all lung cancers and shows a poor prognosis because of its resistance to systemic chemotherapy [1]
There are several types of glucose transporters (GLUTs), glucose transporter 1 (GLUT1) and GLUT3 are strongly expressed on the membrane of tumor cells, and a meta-analysis demonstrated GLUT1 to be a prognostic marker for predicting worse outcomes in patients with lung cancer [4]. 18F-FDG accumulates in tumor cells via GLUT1, a process closely associated with poor prognosis and tumor progression in patients with lung cancer [5]
We previously showed that 18F-FDG uptake in PPC is closely related to the presence of GLUT1 and angiogenesis, and that the accumulation of 18F-FDG and the expression level of GLUT1 were significantly higher in patients with PPC than those with other nonsmall cell lung cancer (NSCLC) [6]
Summary
Pulmonary pleomorphic carcinoma (PPC) is a rare disease with an incidence of 0.1%–0.4% among all lung cancers and shows a poor prognosis because of its resistance to systemic chemotherapy [1]. 18F-FDG accumulates in tumor cells via GLUT1, a process closely associated with poor prognosis and tumor progression in patients with lung cancer [5]. We previously showed that 18F-FDG uptake in PPC is closely related to the presence of GLUT1 and angiogenesis, and that the accumulation of 18F-FDG and the expression level of GLUT1 were significantly higher in patients with PPC than those with other nonsmall cell lung cancer (NSCLC) [6]. This indicates that tumor glucose metabolism involving GLUT1 plays a crucial role in the carcinogenesis of PPC. We examined the prognostic role of GLUT1 expression in patients with surgically resected PPC
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