Glutathione S-transferases as molecular markers of tumour progression and prognosis in renal cell carcinoma

Histopathology. 2011 Jan;58(2):180-90. doi: 10.1111/j.1365-2559.2010.03733.x. Epub 2011 Jan 24.

Abstract

Aims: Renal cell carcinoma (RCC) often recurs as distant metastasis; there is thus a need for new indicators to identify high-risk patients. Glutathione S-transferases (GST)-α and -π are involved in the renal bioactivation of toxic metabolites. The aim was to investigate whether their expression is of diagnostic and prognostic value.

Methods and results: Western blotting of microdissected normal kidney and immunostaining of histological RCC microarrays shows expression of GST-α in proximal tubular cells, while GST-π was found in the distal nephron. Of the primary 174 RCC cases examined, GST-α immunoreactivity was restricted to conventional RCC (n=76, 68% positive) and was not seen in any other RCC subtypes. The cross-tabulation of the GST-α scores with other prognostic indices demonstrated that GST-α immunostaining was significantly more frequent in low-grade tumours (χ(2): P<0.004), and that conventional GST-α-positive RCC patients had a mean disease-free survival of 6.0 years (95% confidence interval 5.33-6.63), compared with 4.7 years (3.54-5.90) in GST-α-negative tumours (Kaplan-Meier survival analysis, P=0.011, log-rank test).

Conclusions: GST-α is a highly specific diagnostic marker for primary conventional RCC, where it is a prognostic marker if grade is omitted from the multivariate analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Carcinoma, Renal Cell / enzymology*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Disease-Free Survival
  • Glutathione Transferase / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Neoplasm Staging
  • Prognosis
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Glutathione Transferase