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This Article Full Text Full Text (PDF) All Versions of this Article: ERC-08-0211v1 16/3/919    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fenske, W. Articles by Fassnacht, M. PubMed PubMed Citation Articles by Fenske, W. Articles by Fassnacht, M.

¹ Endocrine and Diabetic Unit, Department of Internal Medicine I, University Hospital of Würzburg
² Institute of Pathology, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany
³ Department of Gynaecology, University Hospital of Würzburg, Würzburg, Germany
⁴ Department of Internal Medicine I, University Hospital, University of Heidelberg, Heidelberg, Germany

(Correspondence should be addressed to M Fassnacht; Email: fassnacht_m{at}medizin.uni-wuerzburg.de)

^* (W Fenske and H-U Völker contributed equally to this work)

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 metatastic 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.