Expression of structurally unaltered androgen receptor in extramammary Paget's disease.
Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that shows differentiation to an apocrine sweat gland. Although we previously showed that erbB-2 overexpression may play a part in the progression of EMPD, molecular genetic defects underlying the development of EMPD are poorly understood. In the study described here, we examined androgen receptor expression and gene alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen receptor. Semi-quantitation of receptor content by scoring immunostained sections showed no difference between in situ (n = 17) and invasive (n = 13) EMPD tumors. Androgen receptor expression was also observed in four of six lymph node metastases. In these lymph nodes, expression of androgen receptor mRNA was confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing of exon 2 through exon 8, which encodes DNA- and hormone-binding domains of the androgen receptor gene, revealed no mutation in any of the 10 advanced stage tumors. Neither amplification nor deletion of the androgen receptor gene locus was detected by dual color fluorescence in situ hybridization analysis in 14 tumors. The present findings showing frequent expression of structurally unaltered androgen receptor in an advanced stage of EMPD may provide a rational basis for hormone therapy, which is widely used in the treatment of metastatic prostate cancer and androgen receptor-positive breast cancer recurrence.
Fujimoto
A
A
Department of Dermatology, Kanazawa University School of Medicine, Takara-machi, Japan.
Takata
M
M
Hatta
N
N
Takehara
K
K
D000368:Aged; D000369:Aged, 80 and over; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000737:chemistry* / Q000628:therapy; D011944:Receptors, Androgen / Q000032:analysis* / Q000235:genetics; D012878:Skin Neoplasms / Q000737:chemistry* / Q000628:therapy
D011944:Receptors, Androgen