Abstract 5563: Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients

Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis in various cancers as well as with resistance towards chemotherapy. In a previous study we found an association between a high immunohistochemical TIMP-1 protein level and a shorter survival for glioblastoma patients. The aim of the present study was to further evaluate TIMP-1 as a prognostic marker in gliomas by performing TIMP-1 fluorescence in situ hybridization (FISH) and by measuring TIMP-1 in plasma. TIMP-1 FISH analysis was performed on 33 glioblastoma biopsies in order to elucidate if the increased levels of TIMP-1 protein could be explained by gene amplification. Moreover, blood samples were collected from 43 patients (31 gliomas including 21 glioblastomas) prior to brain tumor surgery. The plasma TIMP-1 protein level was measured by ELISA. The results showed TIMP-1 FISH scores between 0.7 and 1.1, suggesting neither amplification nor loss of the TIMP-1 gene. The TIMP-1 level measured in plasma was not significantly higher than the TIMP-1 level measured in healthy matched controls. No correlation was identified between the immunohistochemical TIMP-1 levels and the FISH scores or the plasma TIMP-1 levels. In conclusion, TIMP-1 FISH scores or plasma TIMP-1 levels are without prognostic potential in gliomas. The present study suggests that the high immunohistochemical TIMP-1 protein levels in gliomas are not caused by TIMP-1 gene amplification. Moreover, TIMP-1 in plasma is low and not directly related to the tumor TIMP-1 level found by immunohistochemistry. The study suggests that TIMP-1 immunohistochemistry is the method of choice when using TIMP-1 as a biomarker in gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5563. doi:1538-7445.AM2012-5563