MICRORNA-21 EXPRESSION IN VESTIBULAR SCHWANNOMA: POTENTIAL EFFECT ON GROWTH AND POSSIBLE PROGNOSTIC FACTOR

Abstract

Background: Vestibular schwannomas are benign slow growing tumors arising from VIII cranial nerve. They are potential life threatening benign tumor because of intracranial located. The management could be surgical or conservative, but, left untreated, the tumor preserve the possibility to further growth and complication may arise. The natural history is however not predictable and prognostic factor to select patients manageable conservatively should be studied. The molecular pathways that lead to tumorigenesis and growth are not completely defined and a role could be played by microRNA. Elevated levels of microRNA-21 may contribute to tumor growth by deregulating the tumor suppressor phosphatase (PTEN) and consequent activation of protein kinase B (AKT). Aims: evaluation of microRNA-21 expression and measurement of PTEN levels in vestibular schwannoma specimens, compared with expression in normal nerve tissue, to assess a possible overexpression. A correlation of micorRNA-21 expression with tumor size and growth rate of the tumor, when available, was hypothesized to make a prognostic factor. Methods: collection of vestibular schwannomas and great auricular nerve specimens was done sterilely during surgery and immediately stored at -80°C, until its use. Quantitative real-time PCR was used to assess levels of expression of micro-RNA 21 and mRNA for PTEN. Levels of PTEN protein were assessed with immunohistochemical analysis. A retrospective correlation was done between data obtained and clinical notes of patients: tumor size and growth rate. Results: 31 patients with vestibular schwannoma were studied. MicroRNA-21 was founded overexpressed in all cases when compared with normal nerve tissue. Levels of microRNA-21 were not statistically related with tumor size at time of surgery, but a positive correlation with growth rate was noted in 10 cases in which this data was available. PTEN mRNA was founded in all cases. The PTEN protein levels were low in 10 specimens of 13 in which the data was available, and an inverse correlation with levels of microRNA-21 was noted. Conclusions: The microRNA-21 plays a role in tumor development and in growth regulation also in vestibular schwannoma. MicroRNA- 21 may be a proper molecular target for therapies act to reduce the tumor growth and could represent a prognostic factor in selecting patients manageable with observation or early hearing preservation surgery.