Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast
Autor: | Takuya Moriya, Takanori Ishida, Katsuhiko Ono, Jun Ichi Akahira, Dean B. Evans, Kimako Yoshida, Takashi Suzuki, Hironobu Sasano, Yasuhiro Miki, Hisashi Hirakawa, Rie Shibuya |
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Rok vydání: | 2008 |
Předmět: |
Adult
Spectrometry Mass Electrospray Ionization Cancer Research medicine.medical_specialty Stromal cell 17-Hydroxysteroid Dehydrogenases Endocrinology Diabetes and Metabolism Breast Neoplasms Biology Immunoenzyme Techniques Aromatase Endocrinology Internal medicine Carcinoma medicine Steroid sulfatase Humans RNA Messenger skin and connective tissue diseases neoplasms Aged Aged 80 and over Estradiol Reverse Transcriptase Polymerase Chain Reaction Carcinoma Ductal Breast Dihydrotestosterone Middle Aged Ductal carcinoma medicine.disease Survival Rate body regions Carcinoma Intraductal Noninfiltrating Oncology Sex steroid biology.protein Cancer research Immunohistochemistry Female Steryl-Sulfatase Stromal Cells hormones hormone substitutes and hormone antagonists Chromatography Liquid Follow-Up Studies medicine.drug |
Zdroj: | Endocrine Related Cancer. 15:113-124 |
ISSN: | 1479-6821 1351-0088 |
Popis: | It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast. |
Databáze: | OpenAIRE |
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