title: Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma.
abstract: Owing to the rarity of adrenocortical carcinoma (ACC) no prognostic markers have been established beyond stage and resection status. Accelerated glycolysis is a characteristic feature of cancer cells and in a variety of tumour entities key factors in glucose metabolism like glucose transporter 1 and 3 (GLUT1 and -3), transketolase like-1 enzyme (TKTL1) and pyruvate kinase type M2 (M2-PK) are overexpressed and of prognostic value. Therefore, we investigated the role of these factors in ACC. Immunohistochemical analysis was performed on tissue microarrays of paraffin-embedded tissue samples from 167 ACCs, 15 adrenal adenomas and 4 normal adrenal glands. Expression was correlated with baseline parameters and clinical outcome. GLUT1 and -3 were expressed in 33 and 17% of ACC samples respectively, but in none of the benign tumours or normal adrenals glands. By contrast, TKTL1 and M2-PK were detectable in all benign tissues and the vast majority of ACCs. GLUT1 expression was strongly associated with prognosis in univariate and multivariate analysis (P<0.01), whereas GLUT3, TKTL1 and M2-PK did not correlate with clinical outcome. Patients with strong GLUT1 staining showed a considerably higher overall mortality (hazard ratio (HR) 6.34 (95% confidence interval 3.10-12.90) compared with patients with no GLUT1 staining. When analysing patients in their early stages and advanced disease separately, similar results were obtained. HR for survival was 5.31 (1.80-15.62) in patients with metastatic ACC and in patients after radical resection the HR for disease-free survival was 6.10 (2.16-16.94). In conclusion, GLUT1 is a highly promising stage-independent, prognostic marker in ACC.
authors.affiliation: Endocrine and Diabetic Unit, Department of Internal Medicine I, University Hospital of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fenske
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Völker
authors.forename: Patrick
authors.initials: P
authors.lastname: Adam
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahner
authors.forename: Sarah
authors.initials: S
authors.lastname: Johanssen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wortmann
authors.forename: Melanie
authors.initials: M
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Morcos
authors.forename: Hans-Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D005947:Glucose