Nestin-positive stem cells in neurofibromas from patients with neurofibromatosis type 1-tumorigenic or incidental?

摘要

Background: Recently, we found discrete foci of melanin deposits but diffuse positivity with MART-1/MelanA in a neurofibroma from a patient with neurofibromatosis type 1 (NF1). OBJECTIVES:: To ascertain the frequency of cells that had the capacity for melanogenesis in neurofibromas from patients with NF1. Given that nestin-positive mammalian neural crest cells are potentially capable of forming neurons and Schwann cells, an additional aim was to assess the proportion of nestin-positive cells to test our hypothesis that the frequency of melanogenic cells is a direct function of the stem cell population harbored. METHODS:: Antibodies used included MART-1/MelanA, a transmembrane protein that is present in normal melanocytes and nestin, a type VI intermediate filament protein present in neuronal precursor cells. Seventy-two neurofibromas from 18 patients (10 with multiple and 8 with single) with NF1 were studied. The control group included solitary sporadic neurofibromas from 24 patients. Results: Expression of markers was as follows: MART-1/MelanA staining in 5/72 cases (7%) from neurofibromas from 2/18 patients with NF1 versus 0/24 (0%) in the sporadic neurofibroma group (P = 0.33) and nestin in 33/72 cases (49%) from neurofibromas from 9/18 patients with NF1 versus 3/24 (12.5%) in the sporadic neurofibroma group (P = 0.003). All 5 cases of neurofibroma that were MART-1/MelanA positive also demonstrated positive staining with nestin. Conclusions: Although we found no difference in melanogenic cells in neurofibromas from patients with NF1 relative to the sporadic group, we did find a significant population of nestin-positive progenitor cells in neurofibromas from patients with NF1. In light of recent evidence linking formation of neural neoplasms such as neurofibroma to alterations in the self-renewal program of stem/progenitor cells, our findings reinforce the potentially tumorigenic role of nestin-positive progenitor cells in neurofibromas from patients with NF1.