Sporadic Vestibular Schwannomas Associated With Good Hearing Secrete Higher Levels of Fibroblast Growth Factor 2 Than Those Associated With Poor Hearing Irrespective of Tumor Size

*Program in Speech and Hearing Bioscience and Technology, Harvard Medical School and Massachusetts Institute of Technology, Cambridge
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (Impact Factor: 1.79). 03/2013; 34(4). DOI: 10.1097/MAO.0b013e31828048ec
Source: PubMed


HYPOTHESIS: We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. BACKGROUND: Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. METHODS: Fresh surgical specimens of VS were incubated in sterile PBS at 37°C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition ≥70% and pure-tone average ≤30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). RESULTS: Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. CONCLUSION: This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.

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    ABSTRACT: This study aimed to evaluate the relationship between cochlear signal on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences and hearing in patients undergoing hearing preservation surgery for vestibular schwannoma (VS) and to demonstrate a new classification system to be used in imaging evaluation of patients with VS. A search of archived surgical cases at a single institution between January 1, 2006, and January 1, 2012, revealed 51 patients who underwent hearing preservation surgery for VS. Tumor size, patient age and sex, and preoperative and postoperative pure-tone average (PTA) and speech discrimination score (SDS) were recorded. Cochleae on the affected side were examined on preoperative FLAIR sequences and classified as limited hyperintensity (LH) or extensive hyperintensity (EH). Mean patient age was 51 years, and mean tumor size was 1.3 cm. Preoperative FLAIR sequences were classified into LH (n = 36) and EH (n = 15) categories. Preoperative PTA and SDS were 29.5 dB (SD, 16.7), 90% (SD, 14) and 40.6 dB (SD, 13.8), 80% (SD, 25) for LH and EH, respectively. On univariate analysis, preoperative PTA was superior in the LH group (p = 0.04). There was a trend toward superior preoperative SDS and postoperative PTA in the LH group, but these differences were not statistically significant (p = 0.08 and p = 0.06, respectively). The current study is the first to demonstrate a distinct association between cochlear FLAIR signal and pretreatment hearing levels in patients with VS. A new classification system for evaluating cochlear FLAIR signal is proposed. Improvement in FLAIR sequences will allow further investigation of this association.
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