Glucose transporter GLUT1 expression is an stage-independent predictor of clinical outcome in adrenocortical carcinoma

Endocr Relat Cancer. 2009 Sep;16(3):919-28. doi: 10.1677/ERC-08-0211. Epub 2009 May 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / diagnosis*
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Carcinoma / diagnosis*
  • Adrenocortical Carcinoma / metabolism*
  • Adrenocortical Carcinoma / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 1 / metabolism*
  • Glucose Transporter Type 1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • Glucose