title: Expression levels of melanoma inhibitory activity correlate with time to progression in patients with high-grade glioma.
abstract: Melanoma inhibitory activity (MIA) is related to disease progression in patients with malignant melanoma and to invasion and metastasis of melanoma in vivo and in vitro. An alternative splice product termed MIA(splice) was described recently. In addition to melanoma, both proteins are expressed in a substantial subset of high-grade gliomas. We hypothesize that expression levels of both proteins correlate with early tumor progression and parameters of disseminated disease in patients with high-grade glioma. We examined the correlation of expression levels of MIA and MIA(splice) with time to progression and morphological and clinical markers of disseminated disease (defined as multifocal occurrence, gliomatosis, invasion or metastasis) in a series of 24 newly-diagnosed human high-grade gliomas. Homogenates of surgical specimens, cell cultures and blood samples were analyzed. Significant levels of MIA and MIA(splice) protein were detected in 71% of homogenates of high-grade glioma, but not in the related blood samples. Patients with early tumor progression had lower expression levels of MIA than patients with late progression, and the expression level of MIA was inversely related to time to progression. In addition, MIA expression correlated with a high fiber content of the extracellular matrix, suggesting a role in dissemination as known from malignant melanoma. Expression levels of MIA in homogenates of surgical specimen directly relate to a more benign clinical prognosis in patients with high-grade glioma. While a mechanistic relation has not yet been verified, factors such as a high fiber content of the extracellular matrix may explain this observation.
authors.affiliation: Klinik und Poliklinik fuer Neurologie der Universitaet Regensburg am Bezirksklinikum, 93053 Regensburg, Germany. peter.hau@medbo.de
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.forename: Petra
authors.initials: P
authors.lastname: Ruemmele
authors.forename: Leoni A
authors.initials: LA
authors.lastname: Kunz-Schughart
authors.forename: Anett
authors.initials: A
authors.lastname: Doerfelt
authors.forename: Birgit
authors.initials: B
authors.lastname: Hirschmann
authors.forename: Annette
authors.initials: A
authors.lastname: Lohmeier
authors.forename: Horst
authors.initials: H
authors.lastname: Koch
authors.forename: Adolf
authors.initials: A
authors.lastname: Mueller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000096:biosynthesis; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; D011506:Proteins; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1