Schwannomas, benign tumors with a senescent phenotype.

Abstract

Schwannomas are benign nerve sheath tumors that only very rarely undergo malignant changes. Oncogenic-induced senescence is a defense mechanism against such malignant transformation. Different molecular pathways are involved in this process, such as RAS-RAF-MAPK. Based on the fact that the RAS-RAF-MAPK pathway is known to be activated in peripheral nerve sheath tumors, this study analyzes senescence markers in Schwannomas to demonstrate the possible role of senescence in their genesis. A retrospective immunohistochemical study was done in 39 schwannoma and 18 malignant peripheral nerve sheath tumors (MPNST). Staining for p16INK4a, Ki67, p53 and CyclinD1 was performed in all the cases. Additionally, β-galactosidase staining was done in those cases in which frozen tissue was available (n=8). Higher levels of p16INK4a (p=0.0001) and lower levels of Ki67 (p=0.0001) were found in Schwannomas. Beta-galactosidase activity was positive in 5/5 Schwannomas and negative in 3/3 MPNST. Our results support the senescence nature of Schwannomas and the absence of a senescence phenotype in MPNST.