title: TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.
abstract: Based on the molecular profiling of astrocytomas, we previously identified a series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic astrocytomas relative to diffuse astrocytomas of any histological grade. Although some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas, recent findings challenge this concept. The present study aims to investigate the diagnostic and prognostic values of TIMP-4 and its putative partner CD63 in human astrocytomas. Tissue microarray and image analysis were first carried out to quantitatively analyze the immunohistochemical expression of these proteins in 471 gliomas including 354 astrocytomas. Pathological semi-quantitative scores of both markers' expression were then established and correlated to astrocytoma diagnosis and patient prognosis. TIMP-4 and CD63 expressions were both overexpressed in astrocytomas compared with oligodendrogliomas (P<0.001) and in pilocytic astrocytomas compared with grade II diffuse astrocytomas (P<0.001). In glioblastomas, high TIMP-4/CD63 co-expression scores were identified as independent prognostic factors associated with progression and shorter survival. In conclusion, this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells. It identifies TIMP-4 and CD63 as markers of the astrocytic phenotype in patients with gliomas. In addition, this work highlights the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of patients with glioblastomas.
authors.affiliation: Department of Pathology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Rorive
authors.forename: Xavier Moles
authors.initials: XM
authors.lastname: Lopez
authors.forename: Calliope
authors.initials: C
authors.lastname: Maris
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Trepant
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sauvage
authors.forename: Niloufar
authors.initials: N
authors.lastname: Sadeghi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roland
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D060149:Tetraspanin 30; D046888:Tissue Array Analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C554586:CD63 protein, human