TITLE:
Correlation of Unilateral Sporadic Vestibular Schwannoma Growth Rates with Genetic and Immunohistochemical Abnormalities
AUTHORS:
Atta Mohyuddin, Michael E. Baser, Richard T. Ramsden, D. Gareth R. Evans
KEYWORDS:
Vestibular Schwannoma, NF2 Gene, Immunohistochemistry
JOURNAL NAME:
World Journal of Neuroscience,
Vol.5 No.2,
May
27,
2015
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.