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
Yue
Y
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takeuchi
Satoshi
S
Chen
Shan-Juan
SJ
Dugu
Long
L
Tsuji
Gaku
G
Xie
Lining
L
Nakahara
Takeshi
T
Moroi
Yoichi
Y
Tu
Ya-Ting
YT
Furue
Masutaka
M
D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism*; D010145:Paget Disease, Extramammary / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor