Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival.
In colorectal cancer and breast cancer a high TIMP-1 level has been shown to correlate with a shorter overall patient survival and it has been suggested that TIMP-1 is involved in tumour invasion, proliferation and apoptosis in different types of cancers. TIMP-1 is known to be expressed in gliomas but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1 immunoreactivity of both tumour cells and blood vessels. Moreover, TIMP-1 in situ hybridisation was performed on ten of the glioblastomas. In the vast majority of the tumours TIMP-1 protein was expressed in both tumour cells and blood vessels. In situ hybridisation for TIMP-1 mRNA on glioblastomas confirmed the immunohistochemical expression of TIMP-1. The percentage of TIMP-1 positive tumour cells and blood vessels as well as the staining intensity varied between tumours of the same grade, but the total staining score increased with tumour grade. The multivariate Cox regression test showed that glioblastoma patients with the lowest TIMP-1 expression had a significantly longer overall survival (HR (95% CI) = 3.2 (1.5-6.7), P = 0.004) when compared to the patients with higher TIMP-1 protein expression. In conclusion, this study showed that low TIMP-1 immunohistochemical expression predicts longer overall survival in glioblastoma patients, suggesting a role for TIMP-1 as a biomarker in glioblastoma.
Aaberg-Jessen
Charlotte
C
Department of Pathology, Odense University Hospital, Odense, Denmark. charlotte.aaberg-jessen@ouh.regionsyddanmark.dk.
Christensen
Karina
K
Department of Pathology, Odense University Hospital, Odense, Denmark.
Offenberg
Hanne
H
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Bartels
Annette
A
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Dreehsen
Tanja
T
Department of Pathology, Odense University Hospital, Odense, Denmark.
Hansen
Steinbjørn
S
Department of Oncology, Odense University Hospital, Odense, Denmark.
Schrøder
Henrik Daa
HD
Department of Pathology, Odense University Hospital, Odense, Denmark.
Brünner
Nils
N
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Kristensen
Bjarne Winther
BW
Department of Pathology, Odense University Hospital, Odense, Denmark.
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012044:Regression Analysis; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D019715:Tissue Inhibitor of Metalloproteinase-1