ASSOCIATION OF NEUROTROPHIN RECEPTOR EXPRESSION AND DIFFERENTIATION IN HUMAN NEUROBLASTOMA

Interactions of the trk family of tyrosine kinase receptors with neuro trophins result in growth and maturational changes in neuronal cells. The continued progression, maturation, or regression of neuroblastoma, an embryonal, sympathetic nervous system-derived tumor of infants and children, might be governed by neurotrophic influences. Immunocytoche mistry was utilized to evaluate TrkA, TrkB, and TrkC protein expressio n at the cellular level in the developing human fetal sympathetic nerv ous system and in a selection of neuroblastoma tumor specimens. TrkA a nd TrkC expression was identified in sympathetic ganglia and within th e adrenal medulla, with intense TrkB expression restricted to paragang lia, of the normal developing human sympathetic nervous system. In neu roblastoma, pp140(TrkA) expression correlated positively with favorabl e tumor stage (P = 0.0027) and favorable outcome (P = 0.026). No stati stically significant correlation of TrkC expression with outcome was e vident; however, both trkA and TrkC expression was most apparent in tu mor cells of increased differentiation. TrkB expression was primarily localized to cells within the fibrovascular tumor stroma. A model of n eurotrophin receptor expression and neurotrophin reactivity with diffe rentiation is proposed. The existence and spatial distribution of neur otrophin receptors in neuroblastoma lend supportive evidence that neur otrophic influences may be involved in tumor persistence or regression .