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.
Department of Pathology, Odense University Hospital, Odense, Denmark. charlotte.aaberg-jessen@ouh.regionsyddanmark.dk.
Charlotte
C
Aaberg-Jessen
Department of Pathology, Odense University Hospital, Odense, Denmark.
Karina
K
Christensen
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Hanne
H
Offenberg
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Annette
A
Bartels
Department of Pathology, Odense University Hospital, Odense, Denmark.
Tanja
T
Dreehsen
Department of Oncology, Odense University Hospital, Odense, Denmark.
Steinbjørn
S
Hansen
Department of Pathology, Odense University Hospital, Odense, Denmark.
Henrik Daa
HD
Schrøder
Department of Veterinary Pathobiology, University of Copenhagen, Copenhagen, Denmark.
Nils
N
Brünner
Department of Pathology, Odense University Hospital, Odense, Denmark.
Bjarne Winther
BW
Kristensen
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