gms | German Medical Science

Objective: Vestibular schwannoma (VS) is the most common benign tumor of the cerebellopontine angle. The size of the VS varies widely regardless of the patient's age. While patients with a small, not growing VS undergo regular observational MRI examinations (wait and scan), larger rapidly growing tumors are treated with radiosurgery or promptly removed by microsurgery. Due to the unpredictable growth progression, it is often difficult to determine the optimal time point of surgical intervention. It is well known that tumor stem cells have the ability for self-renewal and an appropriate differentiation potential to generate and support tumor growth. Therefore, the aim of our study is to explore tumor stem cell marker expression and the correlation with tumor growth and volume.

Methods: The study includes 126 adult participants with at least one preoperative MRI image. Patients with recurrence, irradiated VS, or hereditary neurofibromatosis were excluded. First, a comprehensive database was established with various clinical information, for example, patient age, sex, hearing class and KOOS grade of VS. In addition, tumor size was determined by volumetry using preoperative MRI images and growth rate, applicable to patients with multiple preoperative MRI images. RNA was isolated from the tumor samples for quantitative determination of 11 different tumor stem cell markers by quantitative real-time PCR. The relationship between tumor volume, growth rate, KOOS grade and marker expression was analyzed using the Spearman’s rank correlation coefficient.

Results: The data analysis revealed a strong positive correlation between tumor volume and KOOS grade (r=0.89, p<0.05) and between tumor volume and growth rate (r=0.85, p<0.05). Similarly, tumor stem cell markers correlated strongly positively with each other, with 8 of the 11 markers identified correlating moderately positively with KOOS grade and tumor volume of VS (p<0.05). With higher KOOS grade and thus increasing tumor volume, the expression of CXCR-4 (r=0.27), Nanog (r=0.24), CD44 (r=0.25), CD45 (r=0.22), Nestin (r=0.27), Oct-4 (r=0.23), Sall4 (r=0.2) and CD133 (r=0.19) was increased.

Conclusion: The correlation of tumor stem cell markers on the tumor volume of VS indicates that tumor stem cells are involved in tumor growth. This new finding may enable the opportunity to determine a better growth prognosis and identify a drug target that could improve the therapy of VS.