Expression of p75NTR in fetal brain and medulloblastomas: evidence of a precursor cell marker and its persistence in neoplasia

Abstract

p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor superfamily, and plays a significant role in nervous system development. p75NTR has a dual (proliferative/apoptotic) role in neurogenesis and binds pro-neurotrophins with high affinity. Recent work suggests p75NTR is overexpressed in the developing cerebellum and in nodular/desmoplastic medulloblastomas. We analyzed p75NTR expression in various parts of the fetal and adult human central nervous system, and in 75 patients with medulloblastomas. The expression of p75NTR in the fetal brain was seen solely within the external granular layer with weaker expression in the Purkinje layer, which most likely represents Purkinje cell staining. The staining was present in gestational weeks 20-40, while no staining was identified elsewhere in the fetal brain or within the adult cerebellum. p75NTR positive cells were also positive with the proliferation marker ki-67, but were negative for ret, reelin, CD133, CD34, and cleaved caspase 3. Nine of 75 medulloblastomas (12%) were also showed positive immunostaining for p75NTR. The staining was seen in four classic, two desmoplastic, and three anaplastic medulloblastomas. The persistence of p75NTR in a small group of medulloblastomas raises the possibility that in such tumors, the receptor could be a potential therapeutic target.