Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients.
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.
Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark.|Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark.
Charlotte
C
Aaberg-Jessen
Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark.|Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
Bo
B
Halle
Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark.
Stine S
SS
Jensen
DAKO, Glostrup, Denmark.
Sven
S
Müller
Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Unni Maria
UM
Rømer
Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
Christian B
CB
Pedersen
Section of Molecular Disease Biology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nils
N
Brünner
Department of Pathology, Odense University Hospital, Winsløwparken 15, 3. Floor, 5000, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. bjarne.winther.kristensen@rsyd.dk.
Bjarne W
BW
Kristensen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D003718:Denmark; D005260:Female; D005909:Glioblastoma / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000235:genetics*
D019715:Tissue Inhibitor of Metalloproteinase-1
Fluorescence in situ hybridization; Glioblastoma; Glioma; Immunohistochemistry; Plasma; TIMP-1