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

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.