Adhesion Molecule Expression in Primary, Recurrent, and Metastatic Medulloblastomas
D Partridge, SE Croul. University Health Network, Toronto, ON, Canada
Background: Medulloblastoma spreads by leptomeningeal dissemination rather than the infiltration that characterizes other CNS tumors. Adhesion of tumor cells to the meninges is necessary for this spread and may contribute to the survival and proliferation ofthe tumor implants. The mechanisms accounting for this are not known.
Design: This study represents an immunohistochemical study of molecules which may govern medulloblastoma adhesion to leptomeninges. Search of the UHN surgical archives uncovered 57 adult medulloblastomas from 42 patients. In addition to primary resections for all patients, there were 13 recurrences in the posterior fossa and 2 instances of leptomeningeal dissemination. Immunohistochemistry was performed with antibodies to transmembrane adhesion molecules: Beta1 Integrin, NCAM, L1CAM, NCadherin and extracellular matrix molecules: Collagens I and IV, Tenascin, Fibronectin, Vitronectin, Trombospondin and Laminin.
Results: Evaluation of the stained sections showed increased Beta1 Integrin reactivity in recurrent and leptomeningeal tumors compared to their matched primary resections. There was little difference in the reactivity of NCAM, L1CAM and NCadherin between primary and recurrent tumors. Of the extracellular matrix molecules, the greatest difference was seen in Tenascin the staining of which was increased in recurrent tumors.
Conclusions: The current study supports previous in vitro studies from our group (Fiorrilli et al Laboratory Investigation 2008) demonstrating that Beta1 Integrin and Tenascin play critical roles in medulloblastoma adherence to the leptomeningeal extracellular matrix. Further studies in our laboratory will be directed toward elucidating the mechanism by which the expressions of Beta1 Integrin and Tenascin are increaed in these tumors and the importance of that expression to medulloblastoma metastasis.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 199, Tuesday Morning