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

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)-alpha and -pi 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-alpha in proximal tubular cells, while GST-pi was found in the distal nephron. Of the primary 174 RCC cases examined, GST-alpha 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-alpha scores with other prognostic indices demonstrated that GST-alpha immunostaining was significantly more frequent in low-grade tumours (chi 2: P < 0.004), and that conventional GST-alpha-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-alpha-negative tumours (Kaplan-Meier survival analysis, P = 0.011, log-rank test). Conclusions: GST-alpha is a highly specific diagnostic marker for primary conventional RCC, where it is a prognostic marker if grade is omitted from the multivariate analysis.