title: Expression and prognostic value of glucose transporters and hexokinases in tonsil and mobile tongue squamous cell carcinoma.
abstract: The aim of this study was to assess the expression pattern and prognostic value of the high affinity glucose transporters GLUT-1, 3, 4, 8 and 9, SGLT-1 and of hexokinases (HK) I, II and III in squamous cell carcinoma of the tonsil and mobile tongue (TTSCC) by means of immunohistochemistry. Seventy-one consecutive patients suffering from TTSCC were included. The intensity and amount of positive tumour cells in the immunoreaction (histology score (H-score)) for GLUT-1, 3, 4, 8 and 9 as well as for HK-I, II and III were assessed independently by two experienced observers, blinded to the clinical results. H-scores as well as clinical variables were related to patient outcome. Median follow-up time was 49 months (range 1-123 months). Mean H-scores for GLUT expression in decreasing order of magnitude were respectively 10.99 for GLUT-1 (sd 3.9), 5.7 for GLUT-8 (sd 4.0), 5.4 for GLUT-3 (sd 3.7), 1.0 for GLUT-4 (sd 2.0), 1.1 (sd 1.3) for SGLT-1, and 0.4 for GLUT-9 (sd 0.6); GLUT-1 > GLUT-8 = GLUT-3 > GLUT-4 = GLUT-9 = SGLT-1 (with > meaning significantly (p<0.05 on ANOVA + posthoc Bonferroni correction) higher than and =, meaning not significantly different from). Mean H-scores for hexokinase expression were respectively 5.8 for HK-I (sd 3.5), 4.6 for HK-II (sd 3.0) and 2.0 for HK-III (sd 2.0); HK-I > HK-II > HK-III. Finally high H-scores for GLUT-4 were favourably related to disease-free and overall survival on multivariate analysis. To conclude, TTSCC expresses a wide variety of glucose transporter systems and hexokinase enzymes with the "housekeeping" GLUT-1 and HK-I being the most intensely expressed. GLUT-4 over-expression appears to confer a favourable prognosis in squamous cell carcinoma of the tonsil and mobile tongue. Additional studies confirming this finding in larger cohorts of patients are mandatory.
authors.affiliation: Department of Head and Neck Surgery, University Hospital Ghent, Gent, Belgium. philippe.deron@ugent.be
authors.forename: Philippe
authors.initials: P
authors.lastname: Deron
authors.forename: Hubert
authors.initials: H
authors.lastname: Vermeersch
authors.forename: Gilles
authors.initials: G
authors.lastname: Mees
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D051246:Glucose Transport Proteins, Facilitative / Q000032:analysis* / Q000096:biosynthesis*; D006593:Hexokinase / Q000032:analysis* / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000378:metabolism*; D014066:Palatine Tonsil / Q000378:metabolism* / Q000473:pathology*; D010610:Pharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051246:Glucose Transport Proteins, Facilitative; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D006593:Hexokinase