Nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors are overexpressed in extramammary Paget's disease

Background: Neurotrophin (NT) systems appear to play important roles in the pathogenesis of several tumors, but their expression in extramammary Paget's disease (EPD) has not been investigated. Methods: Thirty‐four paraffin‐embedded EPD specimens (32 primary EPD and 2 metastatic to lymph nodes) were subject to immunohistochemical staining for nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), NT3, NT4, their high‐affinity receptors (TrkA, TrkB and TrkC) and the common low‐affinity receptor, p75 NT receptor (p75). Results: All 34 EPD specimens, including 2 metastatic to lymph nodes, showed cytoplasmic overexpression of NGF, BDNF, TrkA and TrkB. The expression (% positive cells) of NGF, BDNF, NT3, NT4, TrkA and TrkB (81.6 ± 14.9, 86.0 ± 10.4, 89.6 ± 14.9, 87.8 ± 17.9, 83 ± 14.4 and 86.2 ± 11.7%) in EPD was significantly higher than in normal skin (21.6 ± 6.5, 27.6 ± 4.5, 19.7 ± 10.1, 8.2 ± 10.0, 25.0 ± 5.3 and 25.4 ± 6.4%), and the expression of these factors in invasive EPD was significantly higher than in noninvasive EPD. Interestingly, Paget cells were negative for p75 and TrkC in all the 34 EPD specimens. Conclusions: These results suggest that overexpression of NGF, BDNF and their high‐affinity receptors (TrkA and TrkB) might play a role in the pathogenesis of EPD. Qian Y, Takeuchi S, Chen S‐J, Dugu L, Tsuji G, Xie L, Nakahara T, Moroi Y, Tu Y‐T, Furue M. Nerve growth factor, brain‐derived neurotrophic factor and their high‐affinity receptors are overexpressed in extramammary Paget's disease.