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Aim: This study analyses the occurrence and distribution of neurotrophins and their receptors in some types of tumours of neural-crest derived cells., Methods and Results: Light microscopy immunohistochemistry associated with quantitative image analysis was used to study the expression of neurotrophins (nerve growth factor, brain-derived neurotrophic factor and neurotrophin (NT)-3) and their cognate receptors (p75(LNGFR), TrkA, TrkB and TrkC) in histologically defined ganglioneuroma, phaeochromocytoma and paraganglioma. The material was fixed in 10% formaldehyde, paraffin-embedded and processed for indirect peroxidase immunohistochemistry using a battery of poly- and monoclonal antibodies to detect neurotrophins and their receptors, as well as some neuronal, endocrine and glial cell markers. A subpopulation of cells in phaeochromocytomas and ganglioneuromas expressed NT-3, but not other neurotrophins, while in paragangliomas no neurotrophins were detected. Regarding neurotrophin receptors, all tumours lacked p75(LNGFR), except for the ganglionic part of a case of mixed phaeochromocytoma, whereas they displayed TrkA (two of two ganglioneuromas, six of nine phaeochomocytomas and three of four paragangliomas). Furthermore, TrkC was regularly detected in a neuronal subpopulation in ganglioneuroma. Interestingly, the percentage of neurones expressing TrkA and TrkC was increased with respect to normal tissues in ganglioneuromas, as well as the percentage of the area occupied by TrkA-immunoreactive cells in the phaeochromocytomas., Conclusion: The pattern of expression of neurotrophins and neurotrophin receptors in the analysed tumours basically matches that of sympathetic neurones, adrenal chromaffin cells and paraganglionic cells, and suggests responsiveness of these cells to neurotrophins. Nevertheless, the function of TrkA and TrkC in regulating the biology of these tumours, if any, remains to be elucidated.

Increasing evidence suggests that some members of the neurotrophic factor family of neurotrophins could be implicated in the regulation of immune responses. Neurotrophins, as well as their tyrosine kinase signal-transducing receptors (the so-called Trk neurotrophin receptors), have been detected in different lymphoid tissues, although their cellular localization is not well known. In this study we used single and double immunohistochemistry to localize TrkB in situ in the rat thymus (in animals from 0 days to 2 years of age), in cytospin preparations of rat thymic cells, and in two mouse monocyte-macrophage cell lines (RAW 264.7 and J774A.1). We found TrkB protein expression in a subpopulation of cells in the corticomedullary junction, which simultaneously expressed the rat macrophage marker ED1. The density of TrkB-expressing cells increased with age, reaching maximal values at 2 years. Conversely, no evidence of TrkB protein expression could be found in dendritic cells, epithelial cells or thymocytes. Thymic macrophages in cytospin preparations, as well as in the mouse monocyte macrophage cell lines, also expressed TrkB protein. Although the possible function of TrkB in the thymic macrophage remains to be clarified, present findings add further evidence to the proposed role of neurotrophins in the immune system.