Apoptosis, neuronal maturation, and neurotrophin expression within medulloblastoma nodules

Nodular/desmoplastic medulloblastomas are a well-established histopathologi cal subtype containing reticulin-free nodules or "pale islands" that are co mprised of cells with round "neurocytic" nuclei and abundant cytoplasm. Sig nificant neuronal maturation occurs within nodules. We used immunohistochem istry to evaluate neuronal differentiation in the nodules of 6 of these: tu mors. The neuronal markers NeuN, synaptophysin, and MAP-2 were identified i n the "pale islands" of all 6 nodular medulloblastomas examined, and high a nd medium molecular weight nonphosphorylated neurofilaments were detected i n 2 of the 6 cases. We also observed collections of apoptotic cells within nodules. Given the known role of neurotrophin signaling in neuronal maturat ion and apoptosis, we analyzed immunohistochemically the distribution of ne urotrophin receptors TrkA and TrkC and their primary ligands NGF and NT3 in 14 nodular medulloblastomas. TrkA and TrkC were detected in 13 and 10 case s, respectively, and were predominantly localized within nodules. NGF and N T3 were distributed diffusely with some nodular accentuation. The localized expression of Trk receptors within nodules of desmoplastic medulloblastoma s suggests neurotrophin signaling is involved in the apoptosis and neuronal differentiation in medulloblastomas. We also examined expression of p53 an d BCL-2 in these tumors, both were prominent in internodular regions but on ly weakly expressed within nodules. Trk receptors, p53, and BCL-2 are all e xpressed during development of the normal cerebellum. interestingly, the im munohistochemical expression profile of these proteins in the differentiati ng nodules of medulloblastomas is in many ways similar to their expression in the developing cerebellum. Thus similar signaling pathways may be operat ional in cerebellar development and medulloblastoma tumor differentiation.