Androgen receptor and 5alpha-reductase immunohistochemical profiles in extramammary Paget disease.
BACKGROUND
Extramammary Paget disease is an uncommon skin tumour occurring mostly in the genitoperineal region. Previous reports have shown frequent expression of androgen receptor, suggesting a tumour-proliferative effect of androgens on Paget cells. Androgen-converting enzymes such as 5alpha-reductase, which locally produces a bioactive androgen, have recently gained attention in studies of the intratumoral actions of androgens.


OBJECTIVE
We investigated correlations between the androgenic microenvironment and invasiveness in extramammary Paget disease, particularly in terms of sex differences.


METHODS
We examined 58 cases of extramammary Paget disease (32 men, 26 women; 42 noninvasive, 16 invasive) using immunohistochemistry for androgen receptor and 5alpha-reductase.


RESULTS
In all 58 cases, expression rates were 57% for androgen receptor and 55% for 5alpha-reductase, with 38% double-positivity for androgen receptor and 5alpha-reductase. Only 5alpha-reductase expression rate was significantly higher in invasive cases (81%) than in noninvasive cases (45%; P = 0.042). For invasive cases, numbers of double-positive results for androgen receptor and 5alpha-reductase were significantly higher in men (70%) than in women (17%; P = 0.039).


CONCLUSIONS
Double positivity for androgen receptor and 5alpha-reductase in Paget cells suggests autocrine synthesis of androgens in extramammary Paget disease. The different hormonal microenvironments in male and female cases and intratumoral androgen levels affect the invasiveness of extramammary Paget disease.
Kasashima
S
S
Department of Pathology, National Hospital Organization, Kanazawa Medical Center, 1-1 Shimoishibikimachi, Kanazawa 920-8650, Japan. sato-kasa@kinbyou.hosp.go.jp
Ozaki
S
S
Kawashima
A
A
Zen
Y
Y
Moriya
T
T
Inoue
M
M
D000368:Aged; D000369:Aged, 80 and over; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D011944:Receptors, Androgen / Q000378:metabolism*; D012737:Sex Factors; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D042944:Cholestenone 5 alpha-Reductase