Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.
Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.
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DOI：
10.1111/cas.12535
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发表时间：
2014-11
期刊：
影响因子：
5.7
通讯作者：
Sasano H
中科院分区：
文献类型：
--
作者：
Yoda T;McNamara KM;Miki Y;Takagi M;Rai Y;Ohi Y;Sagara Y;Tamaki K;Hirakawa H;Ishida T;Suzuki T;Ohuchi N;Sasano H
浸润性小叶癌 (ILC) 约占所有乳腺癌的 10%，其特点是与浸润性导管癌 (IDC) 相比，雄激素受体 (AR) 水平较高。尽管存在这种潜在的雄激素反应环境，但 AR 和雄激素代谢在非肿瘤性小叶和小叶癌中的综合重要性仍然未知。因此，在本研究中，我们使用免疫组织化学方法评估了 178 例 ILC 和周围组织学非肿瘤性小叶组织中关键雄激素生成酶 5 型 17β-羟基类固醇脱氢酶 (17βHSD5) 和 1 型 5α-还原酶 (5αRed1) 的状态。与非肿瘤性小叶相比，ILC 中雄激素受体的患病率较高，但雄激素酶较低。在 ILC 病例中，5αRed1 和 17βHSD5 的状态与肿瘤大小 (P = 0.0053) 和核分级 (P = 0.0290) 呈负相关，并且与患者更好的总生存率显着相关 (P = 0.0059)。基于这些发现，我们假设雄激素信号传导可以充当肿瘤抑制因子。先前的研究表明，雄激素可能通过增加 IDC 组织中雌激素失活酶 2 型 17β-羟基类固醇脱氢酶 (17βHSD2) 的水平来部分发挥作用，因此这被合理地认为是雄激素作用的潜在机制。雄激素酶的状态与 17βHSD2 之间存在显着正相关（P < 0.0001），瘤内 17βHSD2 与 ILC 中的肿瘤大小呈负相关（P = 0.0075）。这些相关性表明雄激素作用的一种保护模式可能是通过调节雌激素代谢。我们目前的研究结果表明，雄激素产生酶可以在富含 AR 的 ILC 病例中发挥关键的保护作用。
Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (P = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen-producing enzymes could play pivotal protective roles in AR-enriched ILC cases.
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绝经后妇女的雄激素受体表达和乳腺癌存活。
DOI：
10.1158/1078-0432.ccr-10-2021
发表时间：
2011-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hu R;Dawood S;Holmes MD;Collins LC;Schnitt SJ;Cole K;Marotti JD;Hankinson SE;Colditz GA;Tamimi RM
通讯作者：
Tamimi RM
影响因子：
3.3
作者：
Ogawa, Yoshinari;Hai, Eishu;Nishiguchi, Yukio
通讯作者：
Nishiguchi, Yukio
影响因子：
5.8
作者：
Sasano, H;Frost, AR;Nagura, H
通讯作者：
Nagura, H
影响因子：
6.2
作者：
Moinfar, F;Okcu, M;Denk, H
通讯作者：
Denk, H
影响因子：
5.8
作者：
Cheng, GJ;Li, Y;Gustafsson, JÅ
通讯作者：
Gustafsson, JÅ