Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

Rie Shibuya, Takashi Suzuki, Yasuhiro Miki, Kimako Yoshida, Takuya Moriya, Katsuhiko Ono, Jun Ichi Akahira, Takanori Ishida, Hisashi Hirakawa, Dean B. Evans, Hironobu Sasano

研究成果: Article査読

67 被引用数 (Scopus)

抄録

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 5α-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 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1)), and androgen-producing enzymes (17βHSD5 and 5α-reductase type 1 (5αRed1)) 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 5αRed1 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.

本文言語English
ページ(範囲)113-124
ページ数12
ジャーナルEndocrine-Related Cancer
15
1
DOI
出版ステータスPublished - 2008 3

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 腫瘍学
  • 内分泌学
  • 癌研究

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