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

摘要

Background: Vestibular schwannomas are benign slow growingudtumors arising from VIII cranial nerve. They are potential lifeudthreatening benign tumor because of intracranial located. Theudmanagement could be surgical or conservative, but, left untreated, theudtumor preserve the possibility to further growth and complication mayudarise. The natural history is however not predictable and prognosticudfactor to select patients manageable conservatively should be studied.udThe molecular pathways that lead to tumorigenesis and growth are notudcompletely defined and a role could be played by microRNA.udElevated levels of microRNA-21 may contribute to tumor growth byudderegulating the tumor suppressor phosphatase (PTEN) andudconsequent activation of protein kinase B (AKT).udAims: evaluation of microRNA-21 expression and measurement ofudPTEN levels in vestibular schwannoma specimens, compared withudexpression in normal nerve tissue, to assess a possible overexpression.udA correlation of micorRNA-21 expression with tumor size and growthudrate of the tumor, when available, was hypothesized to make audprognostic factor.udMethods: collection of vestibular schwannomas and great auricularudnerve specimens was done sterilely during surgery and immediatelyudstored at -80°C, until its use. Quantitative real-time PCR was used toudassess levels of expression of micro-RNA 21 and mRNA for PTEN.udLevels of PTEN protein were assessed with immunohistochemicaludanalysis. A retrospective correlation was done between data obtainedudand clinical notes of patients: tumor size and growth rate.udResults: 31 patients with vestibular schwannoma were studied.udMicroRNA-21 was founded overexpressed in all cases whenudcompared with normal nerve tissue. Levels of microRNA-21 were notudstatistically related with tumor size at time of surgery, but a positiveudcorrelation with growth rate was noted in 10 cases in which this dataudwas available. PTEN mRNA was founded in all cases. The PTENudprotein levels were low in 10 specimens of 13 in which the data wasudavailable, and an inverse correlation with levels of microRNA-21 wasudnoted.udConclusions: The microRNA-21 plays a role in tumor developmentudand in growth regulation also in vestibular schwannoma. MicroRNA-ud21 may be a proper molecular target for therapies act to reduce theudtumor growth and could represent a prognostic factor in selectingudpatients manageable with observation or early hearing preservationudsurgery.