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Aaberg-Jessen C, Halle B, Jensen SS, et al. Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients. J Neurooncol. 2016;130(3):439-448doi: 10.1007/s11060-016-2252-4.
Aaberg-Jessen, C., Halle, B., Jensen, S. S., Müller, S., Rømer, U. M., Pedersen, C. B., Brünner, N., & Kristensen, B. W. (2016). Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients. Journal of neuro-oncology, 130(3), 439-448. https://doi.org/10.1007/s11060-016-2252-4
Aaberg-Jessen, Charlotte, et al. "Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients." Journal of neuro-oncology vol. 130,3 (2016): 439-448. doi: https://doi.org/10.1007/s11060-016-2252-4
Aaberg-Jessen C, Halle B, Jensen SS, Müller S, Rømer UM, Pedersen CB, Brünner N, Kristensen BW. Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients. J Neurooncol. 2016 Dec;130(3):439-448. doi: 10.1007/s11060-016-2252-4. Epub 2016 Sep 12. PMID: 27619981; PMCID: PMC5118392.
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J Neurooncol. 2016 Dec;130(3):439-448. doi: 10.1007/s11060-016-2252-4. Epub 2016 Sep 12.

Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients.

Journal of neuro-oncology

Charlotte Aaberg-Jessen, Bo Halle, Stine S Jensen, Sven Müller, Unni Maria Rømer, Christian B Pedersen, Nils Brünner, Bjarne W Kristensen

Affiliations

  1. Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark.
  2. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
  3. Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
  4. DAKO, Glostrup, Denmark.
  5. Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  6. Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark. [email protected].
  7. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. [email protected].

PMID: 27619981 PMCID: PMC5118392 DOI: 10.1007/s11060-016-2252-4

Abstract

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.

Keywords: Fluorescence in situ hybridization; Glioblastoma; Glioma; Immunohistochemistry; Plasma; TIMP-1

Conflict of interest statement

The authors declare no conflict of interest.

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