title: Expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in skull base chordoma: a series of 145 tumors.
abstract: Chordomas are locally invasive tumors that have a tendency to relapse despite optimal treatment. Specific biological markers might be used to describe their behavior. There is currently no agreement regarding the best way to manage intracranial chordomas. We studied the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in 145 paraffin-embedded tumors. The purpose of our study was to determine: (a) the role of potent angiogenic factors VEGFR-2 and iNOS and their relationship to each other in skull base chordoma and (b) the role of monocytes/macrophages as a potential iNOS source in the angiogenic process. A series of 74 chordoma patients for a total of 145 lesions (including 71 recurrent lesions) and 10 specimens from embryonic notochord were investigated for the expression of iNOS, VEGFR-2, Ki-M1P, and CD-34 using immunohistochemistry. In the majority of the chordomas, correlations were found between iNOS and the immunoreactivity of Ki-M1P (r = 0.5303, P < 0.0001). Furthermore, the expressions of Ki-M1P was correlated with VEGFR-2 (r = 0.4181, P < 0.0001). Our results indicate that chordomas may respond to receptor tyrosine kinase inhibitors such as VEGFR-2 or modulators of other downstream signaling molecules. The future of VEGFR-2 and iNOS inhibitors as therapeutic agents in the treatment of chordoma will be clearer over the next years as results of the current clinical trials become available and as the factors regulating angiogenesis and the interactions between these factors are elucidated. However, appropriate functional experiments remain to be conducted to prove such a hypothesis.
authors.affiliation: Department of Neurosurgery, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany, reza.akhavan-sigari@med.uni-goettingen.de.
authors.forename: R
authors.initials: R
authors.lastname: Akhavan-Sigari
authors.forename: M R
authors.initials: MR
authors.lastname: Gaab
authors.forename: V
authors.initials: V
authors.lastname: Rohde
authors.forename: A
authors.initials: A
authors.lastname: Brandis
authors.forename: H
authors.initials: H
authors.lastname: Tezval
authors.forename: M
authors.initials: M
authors.lastname: Abili
authors.forename: K
authors.initials: K
authors.lastname: von Eckardstein
authors.forename: H
authors.initials: H
authors.lastname: Ostertag
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis; D002817:Chordoma / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000473:pathology; D020556:Neutrophil Infiltration; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D019292:Skull Base Neoplasms / Q000378:metabolism* / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D052247:Nitric Oxide Synthase Type II; D040301:Vascular Endothelial Growth Factor Receptor-2