Cathepsin S expression: An independent prognostic factor in glioblastoma tumours--A pilot study.
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.
Department of Neurosurgery, Royal Victoria Hospital, Belfast, Northern Ireland.
Thomas
T
Flannery
Stephen
S
McQuaid
Caroline
C
McGoohan
Robert S
RS
McConnell
Gordon
G
McGregor
Meenakshi
M
Mirakhur
Peter
P
Hamilton
James
J
Diamond
Gordon
G
Cran
Brian
B
Walker
Christopher
C
Scott
Lorraine
L
Martin
David
D
Ellison
Chirag
C
Patel
Clare
C
Nicholson
David
D
Mendelow
Derek
D
McCormick
Patrick G
PG
Johnston
D014408:Biomarkers, Tumor; D002403:Cathepsins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D011994:Recombinant Proteins / Q000378:metabolism; D015996:Survival Rate
D014408:Biomarkers, Tumor; D011994:Recombinant Proteins; D002403:Cathepsins; C028217:cathepsin S