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Prognostic Significance of Glucose Metabolism as GLUT1 in Patients with Pulmonary Pleomorphic Carcinoma.

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 ¹?F-FDG (2-[¹?F]-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.

SUBMITTER: Imai H

PROVIDER: S-EPMC7074371 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Prognostic Significance of Glucose Metabolism as GLUT1 in Patients with Pulmonary Pleomorphic Carcinoma.

Imai Hisao H Kaira Kyoichi K Endoh Hideki H Imaizumi Kazuyoshi K Goto Yasuhiro Y Kamiyoshihara Mitsuhiro M Kosaka Takayuki T Yajima Toshiki T Ohtaki Yoichi Y Osaki Takashi T Kogure Yoshihito Y Tanaka Shigebumi S Fujita Atsushi A Oyama Tetsunari T Minato Koichi K Asao Takayuki T Shirabe Ken K

Journal of clinical medicine 20200203 2

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, larg ...[more]

PMID: 32028659

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Project description:Background Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small cell lung cancer characterized by high malignancy and a poor prognosis. PPC is associated with a high frequency of postoperative relapse, and shows resistance to chemotherapy. The high malignancy of cancers is associated with genomic instability, which is related to mutations of tumor suppressor genes, such as tumor protein p53 (TP53) and ataxia-telangiectasia mutated (ATM). In addition, signaling pathways involving the oncogenes such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and epidermal growth factor receptor (EGFR) are associated with resistance to chemotherapy. However, the association of PPC with these gene mutations remains unknown. We investigated the impact of TP53, ATM, PIK3CA, and EGFR mutations on the postoperative prognosis of PPC. Methods Fifty-five patients with PPC who underwent complete resection were studied. A gene mutation analysis was performed using next-generation sequencing. Postoperative overall survival of patients with gene mutations was evaluated using a multivariable Cox proportional hazards model in which the explanatory variables were the presence of each gene mutation, and the confounding factors were pathological stage and age. The robustness of the results was evaluated by a sensitivity analysis. Results The frequencies of pathogenic mutations in TP53, ATM, PIK3CA, and EGFR were 47, 0, 7, and 9%, respectively. A multivariable analysis adjusted for pathological stage and age showed a significant difference for only PIK3CA mutations. The hazard ratio (HR) for overall survival in cases with pathogenic mutations of PIK3CA for wild type or non-pathogenic mutations was 4.5 (95% confidence interval [CI] 1.1–18.8). Likewise, sensitivity analyses adjusted for pathological stage and sex (HR, 7.5; 95% CI 1.7–32.4) and for age and sex (HR, 5.4; 95% CI 1.4–21.7) resulted in similar findings. Although three patients with pathogenic mutations of PIK3CA that recurred postoperatively were treated by chemotherapy or immunotherapy, they survived for less than 2 years. Conclusions The postoperative prognosis of PPC with PIK3CA pathogenic mutations is particularly poor. Pathogenic mutations of PIK3CA may be a postoperative prognostic marker. Inhibition of signaling pathways associated with PIK3CA mutations may also be a target for chemotherapy after relapse of PPC. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-10176-4.

Dataset Information

Prognostic Significance of Glucose Metabolism as GLUT1 in Patients with Pulmonary Pleomorphic Carcinoma.

Publications

Prognostic Significance of Glucose Metabolism as GLUT1 in Patients with Pulmonary Pleomorphic Carcinoma.

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