Schwannomas, bening tumors with a senescent phenotype

S. Simonetti^1,3*, C. Serrano^2,3*, J. Hernández-Losa^1,3, S. Bagué^3,4, R. Orellana^3,5, C. Valverde², M.E. Lleonart¹, M. Aizpurua¹, J. Carles², S. Ramón y Cajal^1,3+ and C. Romagosa^1,3+

¹Pathology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain, ²Oncology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain, ³Universitat Autonoma de Barcelona, Barcelona, Spain, ⁴Pathology Department, Hospital de San Pau, Barcelona, Spain and ⁵Pathology Department, Hospital Parc Taulí, Sabadell, Barcelona, Spain
*Both authors contributed equally to this work
⁺Both authors contributed equally to this work

Offprint requests to: Santiago Ramón y Cajal and Cleofé Romagosa, Pathology Department, Fundació Institut de Recerca, Hospital Universitari Vall d´Hebrón, Passeig de la Vall d-Hebron 119-129, 08035 Barcelona, Spain. e-mail: sramon@vhebron.net and cromagos@vhebron.net


Summary. Background: 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. Methods: A retrospective immunohistochemical study was done in 39 schwannoma and 18 malignant peripheral nerve sheath tumors (MPNST). Staining for p16^INK4a, Ki67, p53 and CyclinD1 was performed in all the cases. Additionally, ß-galactosidase staining was done in those cases in which frozen tissue was available (n=8). Results: Higher levels of p16^INK4a (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. Conclusions: Our results support the senescence nature of Schwannomas and the absence of a senescence phenotype in MPNST. Histol Histopathol 29, 721-730 (2014)

Key words: Schwannomas, MPNST, Senescence, p16^INK4a

DOI: 10.14670/HH-29.721