Neurotrophins and neurotrophin receptors in some neural crest-derived tumours (ganglioneuroma, phaeochromocytoma and paraganglioma)

Aims: 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 neurotrophi ns (nerve growth factor, brain-derived neurotrophic factor and neurotrophin (NT)-3) and their cognate receptors (p75(LNGFR) TrkA, TrkB and TrkC) in hi stologically defined ganglioneuroma, phaeochromocytoma and paraganglioma. T he material was fixed in 10% formaldehyde? paraffin-embedded and processed for indirect peroxidase immunohistochemistry using a battery of poly- and m onoclonal antibodies to detect neurotrophins and their receptors, as well a s some neuronal, endocrine and glial cell markers. A subpopulation of cells in phaeochromocytomas and ganglioneuromas expressed NT-3, but not other ne urotrophins, while in paragangliomas no neurotrophins were detected. Regard ing neurotrophin receptors, all tumours lacked Nevertheless, the function o f TrkA and TrkC in regulating the biology of these tumours, if any, remains to be elucidated. p75(LNGFR) except for the ganglionic part of a case of m ixed phaeochromocytoma, whereas they displayed TrkA (two of two ganglioneur omas, six of nine phaeochromocytomas and three of four paragangliomas). Fur thermore, TrkC was regularly detected in a neuronal subpopulation in gangli oneuroma. Interestingly, the percentage of neurones expressing TrkA and Trk C 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 rec eptors in the analysed tumours basically matches that of sympathetic neuron es, adrenal chromaffin cells and paraganglionic cells, and suggests respons iveness 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.