A high TIMP-1 level has earlier been shown to be related to shorter survival in colorectal cancer and breast cancer suggesting that TIMP-1 might be an important prognostic biomarker. It has been suggested that TIMP-1 is involved in tumor invasion, proliferation and apoptosis in different types of cancers. Whether TIMP-1 is a prognostic marker in gliomas has not yet been investigated, although TIMP-1 is known to be expressed in gliomas. The aim of the present study was to investigate the immunohistochemical expression of TIMP-1 in gliomas and relate this expression to patient survival. We used a new TIMP-1 monoclonal antibody (VT-7) on formalin-fixed paraffin-embedded tumor tissue from 23 diffuse astrocytomas, 17 anaplastic astrocytomas and 72 glioblastomas. The staining of tumor cells and vessels were scored and compared with patient overall survival. Moreover TIMP-1 in situ hybridisation was performed on selected glioblastomas. The results showed that TIMP-1 protein was expressed in the vast majority of tumors being expressed in both tumor cells and vessels and in both central and invasive areas of the tumors. In situ hybridization for TIMP-1 mRNA on glioblastomas confirmed the expression of TIMP-1 protein. The fraction of stained tumor cells and vessels as well as the staining intensity varied between tumors of the same grade, but the mean staining score increased with tumor grade. The overall survival of glioblastoma patients was divided into four groups based on TIMP-1 score (0–5, 6–7, 8–9 or 10–12). The multivariate Cox regression test showed that patients with the lowest TIMP-1 expression (score 0–5; n=12) had a significantly longer overall survival (p=0.004). There was no significant correlation between TIMP-1 expression and overall survival for diffuse and anaplastic astrocytomas. In conclusion, the study shows that TIMP-1 immunohistochemical score is significantly associated with overall survival in glioblastoma patients, suggesting that TIMP-1 could be used as a new biomarker for this type of cancer. The shorter survival of patients with high TIMP-1 protein expression may be explained by the anti-apoptotic effect of TIMP-1 preventing apoptosis induced by radiation and chemotherapy. Accordingly, TIMP-1 or TIMP-1 interacting proteins could represent new targets in future anti-cancer therapy.
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Document Type: Abstract
Afdeling for Klinisk Patologi, Odense Universitetshospital, Winsløwparken 15, 5000 Odense C
Afdeling for Almen Patologi, Institut for Veterinær Patobiologi, Det Biovidenskabelige Fakultet, Københavns Universitet, Ridebanevej 9, 1870 Frederiksberg C
Publication date: May 1, 2008