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

Lydia Searchfield, Sally A. Price, Graham Betton, Bharat Jasani, Daniela Riccardi, David F.R. Griffiths

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18 Citations (Scopus)

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 (χ2: P<0.004), and that conventional GST-α-positive RCC patients had a mean disease-free survival of 6.0years (95% confidence interval 5.33-6.63), compared with 4.7years (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.

Original languageEnglish
Pages (from-to)180-190
Number of pages11
JournalHistopathology
Volume58
Issue number2
DOIs
Publication statusPublished - Jan 1 2011

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Keywords

  • 3,3'-diaminobenzidine
  • Glutathione S-transferases
  • Horseradish peroxidase
  • Immunohistochemistry
  • Prognostic indicators
  • Renal cell carcinoma
  • Tissue microarray
  • Western blotting

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Searchfield, L., Price, S. A., Betton, G., Jasani, B., Riccardi, D., & Griffiths, D. F. R. (2011). Glutathione S-transferases as molecular markers of tumour progression and prognosis in renal cell carcinoma. Histopathology, 58(2), 180-190. https://doi.org/10.1111/j.1365-2559.2010.03733.x