PMID- 27619981 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20181113 IS - 1573-7373 (Electronic) IS - 0167-594X (Print) IS - 0167-594X (Linking) VI - 130 IP - 3 DP - 2016 Dec TI - Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients. PG - 439-448 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been associated with poor prognosis and resistance towards chemotherapy in several cancer forms. In a previous study we found an association between a low TIMP-1 tumor immunoreactivity and increased survival for glioblastoma patients, when compared to moderate and high TIMP-1 tumor immunoreactivity. The aim of the present study was to further evaluate TIMP-1 as a biomarker in gliomas by studying TIMP-1 gene copy numbers by fluorescence in situ hybridization (FISH) on 33 glioblastoma biopsies and by measuring levels of TIMP-1 in plasma obtained pre-operatively from 43 patients (31 gliomas including 21 glioblastomas) by enzyme-linked immunosorbent assay (ELISA). The results showed TIMP-1 gene copy numbers per cell ranging from 1 to 5 and the TIMP-1/CEN-X ratio ranging between 0.7 and 1.09, suggesting neither amplification nor loss of the TIMP-1 gene. The TIMP-1 protein levels measured in plasma were not significantly higher than TIMP-1 levels measured in healthy subjects. No correlation was identified between TIMP-1 tumor cell immunoreactivities and the TIMP-1 gene copy numbers or the plasma TIMP-1 levels. In conclusion, high immunohistochemical TIMP-1 protein levels in glioblastomas were not caused by TIMP-1 gene amplification and TIMP-1 in plasma was low and not directly related to tumor TIMP-1 immunoreactivity. The study suggests that TIMP-1 immunohistochemistry is the method of choice for future clinical studies evaluating TIMP-1 as a biomarker in glioblastomas. FAU - Aaberg-Jessen, Charlotte AU - Aaberg-Jessen C AD - Department of Pathology, Odense University Hospital, Winslowparken 15, 3. Floor, 5000, Odense, Denmark. AD - Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. FAU - Halle, Bo AU - Halle B AD - Department of Pathology, Odense University Hospital, Winslowparken 15, 3. Floor, 5000, Odense, Denmark. AD - Department of Neurosurgery, Odense University Hospital, Odense, Denmark. FAU - Jensen, Stine S AU - Jensen SS AD - Department of Pathology, Odense University Hospital, Winslowparken 15, 3. Floor, 5000, Odense, Denmark. FAU - Muller, Sven AU - Muller S AD - DAKO, Glostrup, Denmark. FAU - Romer, Unni Maria AU - Romer UM AD - Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Pedersen, Christian B AU - Pedersen CB AD - Department of Neurosurgery, Odense University Hospital, Odense, Denmark. FAU - Brunner, Nils AU - Brunner N AD - Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Kristensen, Bjarne W AU - Kristensen BW AD - Department of Pathology, Odense University Hospital, Winslowparken 15, 3. Floor, 5000, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk. AD - Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160912 PL - United States TA - J Neurooncol JT - Journal of neuro-oncology JID - 8309335 RN - 0 (Tissue Inhibitor of Metalloproteinase-1) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Brain Neoplasms/*blood/*genetics MH - Cohort Studies MH - DNA Copy Number Variations MH - Denmark MH - Female MH - Glioblastoma/*blood/*genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Tissue Array Analysis MH - Tissue Inhibitor of Metalloproteinase-1/*blood/*genetics PMC - PMC5118392 OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Glioblastoma OT - Glioma OT - Immunohistochemistry OT - Plasma OT - TIMP-1 COIS- The authors declare no conflict of interest. EDAT- 2016/09/14 06:00 MHDA- 2018/01/03 06:00 PMCR- 2016/09/12 CRDT- 2016/09/14 06:00 PHST- 2016/01/19 00:00 [received] PHST- 2016/08/21 00:00 [accepted] PHST- 2016/09/14 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] PHST- 2016/09/14 06:00 [entrez] PHST- 2016/09/12 00:00 [pmc-release] AID - 10.1007/s11060-016-2252-4 [pii] AID - 2252 [pii] AID - 10.1007/s11060-016-2252-4 [doi] PST - ppublish SO - J Neurooncol. 2016 Dec;130(3):439-448. doi: 10.1007/s11060-016-2252-4. Epub 2016 Sep 12.