Vestibular Schwannoma Volume and Tumor Growth Correlates with Macrophage Marker Expression

SIMPLE SUMMARY: The variable growth behavior of vestibular schwannomas (VS) makes therapy decisions very difficult. These benign tumors, which originate from the eighth cranial nerve, partly show a very slow growth rate over many years. Nevertheless, VS can lead to severe symptoms such as hearing loss and dizziness within a short time due to their increase in size. Despite numerous preliminary studies, no apparent influencing factor on size progression could be found so far. In our study, we consider the influence of growth factors and macrophage markers on the volume and growth rate of VS. While growth factors show no effect on tumor growth, higher expression of macrophage markers indicates an infiltration of macrophages. They may thus enhance the growth of VS and therefore represent a potential therapeutic target. ABSTRACT: Vestibular schwannoma is the most common benign tumor of the cerebellopontine angle and originates from Schwann cells surrounding the vestibulocochlear nerve. Since the size of the VS varies widely, affected patients suffer from symptoms of varying severity. It is often difficult to determine the optimal time for therapy, due to the unpredictability of the growth rate. Despite many investigations on influencing factors, no mechanism responsible for the increase in the growth rate of certain VS has been identified so far. Therefore, the present study investigates the influence of the seven markers: Ki-67, cyclooxygenase 2 (COX2), vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), CD163, and CD68 on tumor progression and tumor size in a cohort of 173 VS. The markers were determined by quantitative PCR and correlated with tumor volume and VS growth rate. The analysis showed a significantly negative correlation of the Ki-67, COX2, and VEGF on tumor volume. Moreover, with a higher volume of VS, the expression of the macrophage markers CD68, CD163, and GM-CSF increased significantly. Our results suggest that the increase in VS size is not primarily due to Schwann cell growth but to an infiltration of macrophages. This may have an impact on non-invasive therapy to preserve the hearing function of affected patients.