Tumor miRNA expression profile is related to vestibular schwannoma growth rate.

OBJECTIVE: Our objective was to investigate if the tumor microRNA (miRNA) expression profile was related to tumor growth rate. Growth-related miRNAs might be potential targets for future therapeutic intervention. MATERIAL AND METHODS: Tumor tissue was sampled during surgery of patients with a sporadic vestibular schwannoma. Tumor growth rate was determined by tumor measurement on the two latest pre-operative MRI scans. Tumor miRNA expression was analyzed using the Affymetrix Gene Chip® protocol, and CEL files were generated using GeneChip® Command Console® Software and normalized using Partek Genomics Suite 6.5. The CEL files were analyzed using the statistical software program R. Principal component analysis, affected gene ontology analysis, and analysis of miRNA expression fold changes were used for analysis of potential relations between miRNA expression profile and tumor growth rate. RESULTS AND CONCLUSION: Tumor miRNA expression is related to the growth rate of sporadic vestibular schwannomas. Rapid tumor growth is associated with deregulation of several miRNAs, including upregulation of miR-29abc, miR-19, miR-340-5p, miR-21, and miR-221 and downregulation of miR-744 and let-7b. Gene ontologies affected by the deregulated miRNAs included neuron development and differentiation, gene silencing, and negative regulation of various biological processes, including cellular and intracellular signaling and metabolism.

Extended Retrolabyrinthine Approach: Results of Hearing Preservation Surgery Using a New System for Continuous Near Real-time Neuromonitoring in Patients With Growing Vestibular Schwannomas.

OBJECTIVE: To report hearing preservation results after retrolabyrinthine vestibular schwannoma surgery, using a new system for continuous near real-time monitoring of cochlear nerve function. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center, University Hospital. PATIENTS: Thirty-one consecutive patients with growing vestibular schwannomas and opting for hearing preservation surgery. INTERVENTIONS: Tumor removal by a modified, extended retrolabyrinthine approach, using a new system for continuous near real-time monitoring of cochlear nerve function. MAIN OUTCOME MEASURES: Pure-tone average and speech discrimination (SD) 1-year postoperative. Preservation of word recognition score class. Preservation of serviceable hearing (SD>50%). RESULTS: Any hearing was preserved in 83 and 69% had preserved word recognition score class or better. Serviceable hearing was preserved in 77%. SD was unchanged in 48%, improved in 21%, and poorer in 31%. Of 18 patients with potential for improvement (SD 90% or worse preoperatively), 33% improved (SD increase 10% or more). CONCLUSION: The hearing preservation rate is favorable using the modified, extended retrolabyrinthine approach and a new system for continuous near real-time monitoring of cochlear nerve function for removal of growing vestibular schwannomas, as 77% preserved serviceable hearing 1 year after surgery. Hearing improved after surgery in 33%. Using the new neuromonitoring system, serviceable hearing preservation rate improved from 53 to 77% at our center.

[Workup and treatment of vestibular schwannomas].

Vestibular schwannomas are benign tumours originating from the eighth cranial nerve. The incidence in Denmark is rising and is around 200 per million per year. Pure tone audiometry, discrimination score and tinnitus anamnesis determine, whether a diagnostic MRI is merited. Around one fourth of newly diagnosed patients receive surgery due to the size of the tumour, whereas the remaining three fourths go into a "wait-and-scan" regime. 30-40% of the patients in this regime experience growth and are offered either surgery or radiotherapy.

Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas.

The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (><0.5 ccm/year), employing a p-value <0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.