Hypoxia-Inducible Factor-1α and CD271 inversely correlate with melanoma invasiveness

Melanoma is characterized, among other features, by microenvironmental factors and by an altered apoptotic machinery. Melanoma cell response to a hypoxic environment is transcriptionally regulated by the Hypoxia-Inducible Factor (HIF)-1α. p75 neurotrophin receptor (p75^NTR), also called CD271, mediates apoptosis in several cell systems. The purpose of this study was to analyze the expression of HIF-1α and CD271 in melanomas at different phases of progression, as evaluated by histology and reflectance confocal microscopy (RCM). By RCM, 41.67% tumors were characterized by the presence of a population of dendritic and pleomorphic cells (D+P), corresponding to in situ melanoma; 25% exhibited a predominantly round-cell (RN) proliferation with histologic features of superficial melanoma, and 33.33% showed the presence of cells aggregated in nests (DN), typical of invasive melanoma. HIF-1α was scarcely detected in D+P and in RN melanomas, while it was highly expressed in DN tumors. By contrast, CD271 positive cells were mostly detected in D+P population, and barely observed in the other subtypes. This work demonstrates that CD271 expression inversely correlates with hypoxia in melanoma, and that the two markers may be used in the future as diagnostic/prognostic tools for this neoplasm.