Cathepsin S expression: An independent prognostic factor in glioblastoma tumours - A pilot Study

Christopher Scott, T. Flannery, S. McQuaid, Caroline McGoohan, R.S. McConnell, Gordon McGregor, M. Mirakhur, Peter Hamilton, James Diamond, Gordon Cran, Brian Walker, Lorraine Martin, D. Ellison, C. Patel, C. Nicholson, D. Mendelow, D. McCormick, Patrick Johnston

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175–82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I–III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high-CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti-invasive therapy.
Original languageEnglish
Pages (from-to)854-860
Number of pages7
JournalInternational Journal of Cancer
Volume119
Issue number4
DOIs
Publication statusPublished - 15 Aug 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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