THE STROMAL SCHWANN-CELL DURING MATURATION OF PERIPHERAL NEUROBLASTOMAS - IMMUNOHISTOCHEMICAL OBSERVATIONS WITH ANTIBODIES TO THE NEURONAL CLASS-III BETA-TUBULIN ISOTYPE (BETA-III) AND S-100 PROTEIN

This immunohistochemical study compares the localization of the neuron al class III beta-tubulin isotype (betaIII; analogous to the beta'1-/b eta2-tubulin isoform) to the Schwann cell-associated S-100 protein foc using on topographic relationships of Schwann-like cells to differenti ating neuronal phenotypes during stromal development in human peripher al neuroblastomas. The earliest appearance of Schwann cells in poorly differentiated (classical) neuroblastomas is heralded by S-100 protein -immunoreactive cells in close association with tumor blood vessels. I n subsequent stages of maturation, i.e. maturing neuroblastoma (gangli oneuroblastoma and gangliocytoma), S-100 protein-positive cells are mo stly confined to the connective tissue septa dividing tumor into lobul es, and are not freely interspersed with betaIII-immunoreactive neopla stic neurons. Significant ensheathment of individual axon-like process es by Schwann cells occurs only in mature ganglioneuromas. BetaIII is localized in a full spectrum of neoplastic neuronal phenotypes, rangin g from poorly-differentiated apolar neuroblasts (often signaling ensui ng neuritogenesis) to mature ganglion cells, but not in Schwann cells, or other cell types of the stroma. Our observations suggest that Schw ann cells in peripheral neuroblastomas are stroma-derived cells and no t an expression of divergent neoplastic differentiation.