Glutathione S-transferases as molecular markers of tumor sub-type and prognosis in clinically confined 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) -α and -π are involved in the renal bioactivation of toxic metabolites. We investigated whether their expression could hold 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 sub-types. 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 (χ2: p < 0.004), and that conventional GST-α positive RCC patients had a mean disease-free survival of 6.0 years (95% CI 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.