Abstract
Background: Unilateral sporadic vestibular schwannomas (USVS) are caused by inactivating somatic mutations of both alleles of the neurofibromatosis 2 (NF2) tumor suppressor gene. Unilateral sporadic vestibular schwannomas have a widely-varying growth patterns whose causes are poorly understood. Objective: We examined the relationships between an index of USVS growth, and genetic abnormalities and pathological growth indices. Subjects and Methods: Single-strand conformational polymorphism analysis and heteroduplex methods were used to screen for mutations in all 17 exons of the NF2 gene in USVS from 63 patients. Loss of heterozygosity (LOH) analyses were also carried out. An index of USVS growth (clinical growth index, CGI) was calculated as maximum tumor diameter divided by duration of symptoms. The immunohistochemical growthindices were based on monoclonal antibodies to Ki-67 and another tumor cell proliferation marker (platelet-derived growth factor (PDGF)). Results: CGI was highly variable and did not significantly decrease with increasing age at diagnosis. Either somatic NF2 mutations or LOH was found in 88% of tumors. PDGF and Ki-67 increased significantly with increasing age at diagnosis, and PDGF was lower in tumors with LOH than in those without LOH. In multiple linear regression analysis, CGI was significantly higher in people with higher PDGF, after accounting for age at diagnosis and LOH. Conclusion: An index of USVS growth increases with increasing PDGF, after accounting for age and LOH.
Highlights
Acoustic neuromas or vestibular schwannomas are intracranial, extra-axial tumors that arise from the Schwann cell sheath investing either the vestibular or cochlear nerve
The great majority of VS are unilateral sporadic vestibular schwannomas (USVS), which usually develop between ages 40 and 60
Either a somatic neurofibromatosis 2 (NF2) mutation or Loss of heterozygosity (LOH) were found in 88% of the tumors; both mutational hits were identified in 34 (52%) of tumors and one mutational hit in 23 (35%) of tumors
Summary
Acoustic neuromas or vestibular schwannomas are intracranial, extra-axial tumors that arise from the Schwann cell sheath investing either the vestibular or cochlear nerve. Acoustic neuromas account for approximately 80% of tumors found within the cerebellopontine angle [1]. Diagnosed vestibular schwannomas occur in 0.7 - 1.0 people per 100,000 population. The great majority of VS are unilateral sporadic vestibular schwannomas (USVS), which usually develop between ages 40 and 60. Unilateral sporadic vestibular schwannomas (USVS) are caused by inactivating somatic mutations of both alleles of the neurofibromatosis 2 (NF2) tumor suppressor gene. Unilateral sporadic vestibular schwannomas have a widely-varying growth patterns whose causes are poorly understood. Results: CGI was highly variable and did not significantly decrease with increasing age at diagnosis. In multiple linear regression analysis, CGI was significantly higher in people with higher PDGF, after accounting for age at diagnosis and LOH. Conclusion: An index of USVS growth increases with increasing PDGF, after accounting for age and LOH
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