title: Differential expression and prognostic significance of GLUT1 according to histologic type of non-small-cell lung cancer and its association with volume-dependent parameters.
abstract: We evaluated glucose transporter type 1 (GLUT1) and carbonic anhydrase IX (CAIX) expression, together with volume-based18F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters, in non-small cell lung cancer (NSCLC) patients, and examined the prognostic significance of those parameters according to its histologic subtype.
  
  
  
  A total of 269 patients, who underwent surgical resection for NSCLC, were reviewed retrospectively. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values were measured by preoperative18F-fluorodeoxyglucose positron emission tomography computed tomography. GLUT1 and CAIX expression was evaluated using immunohistochemical method.
  
  
  
  The mean MTV and TLG values were 30.0±57.1 and 165.4±361.3, respectively, and were significantly higher in patients with squamous cell carcinoma than with adenocarcinoma (p=0.047 for MTV; p=0.042 for TLG). GLUT1 expression was identified in 99% of squamous cell carcinoma and 50% of adenocarcinoma patients. MTV and TLG values were significantly higher in GLUT1-positive than GLUT-negative adenocarcinomas; however, CAIX expression did not show this pattern. GLUT1-positive adenocarcinoma patients had a lower OS than GLUT1-negative patients (p<0.001), whereas CAIX-positive and CAIX-negative patients showed similar OS rates (p=0.226). Patients with high MTV and TLG values showed lower OS rates than those with low MTV and TLG values. Multivariate analysis showed that GLUT1 positivity was an independent risk factor for a lower OS rate in lung adenocarcinoma patients (hazard ratio=2.574, p=0.016). GLUT1 expression was associated with micropapillary/solid histology, lymphovascular invasion, and advanced pTNM stage.
  
  
  
  MTV and TLG values, and GLUT1 expression, significantly differed between patients with squamous cell carcinoma and adenocarcinoma. High GLUT1 expression levels were significantly associated with MTV and TLG values and adverse clinical outcomes in patients with adenocarcinoma.
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Young Wha
authors.initials: YW
authors.lastname: Koh
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, 206 Worldcup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Republic of Korea. Electronic address: suesj202@ajou.ac.kr.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, 206 Worldcup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Republic of Korea. Electronic address: psy1117@hanmail.net.
authors.forename: Seong Yong
authors.initials: SY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000071231:Carbonic Anhydrase IX / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D013534:Survival; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
chemical_list: D051272:Glucose Transporter Type 1; D019788:Fluorodeoxyglucose F18; D000071231:Carbonic Anhydrase IX
keywords: CAIX; GLUT1; Metabolic tumor volume; Non-small cell lung cancer; Total lesion glycolysis