Intracrine steroid production and mammalian target of rapamycin pathways in pulmonary lymphangioleiomyomatosis

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• 作者：Koko Adachi ; MD^a ; ^b ; Yasuhiro Miki ; DVM ; PhD^a ; Ryoko Saito ; MD ; PhD^a ; Shuko Hata ; PhD^a ; Masanori Yamauchi ; MD ; PhD^b ; Yoshiki Mikami ; MD ; PhD^c ; ¹ ; Yoshinori Okada ; MD ; PhD^d ; Kuniaki Seyama ; MD ; PhD^e ; Takashi Kondo ; MD ; PhD^d ; Hironobu Sasano ; MD ; PhD^a ; ^{hsasano@patholo2.med.tohoku.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Aromatase ; Bcl-2 ; Estrogen ; mTOR ; Pulmonary lymphangioleiomyomatosis
• 刊名：Human Pathology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：46
• 期：11
• 页码：1685-1693
• 全文大小：1329 K

文摘

Lymphangioleiomyomatosis (LAM) is a rare, potentially fatal disease primarily affecting young women. Estrogens enhance cell proliferation and progression of the tumor. Clinical trials using molecularly targeted agents such as endocrine manipulation and mammalian target of rapamycin (mTOR) inhibitors are in progress, but the status of these molecules, including aromatase and mTOR, has not been explored in LAM tissue. We first examined immunoreactivity for sex steroid receptors (estrogen receptor [ER] 伪, ER尾, progesterone receptor, androgen receptor), sex steroid–synthesizing enzymes (aromatase, steroid sulfatase, 17尾-hydroxysteroid dehydrogenase 1, 5伪-reductases), apoptotic suppression factor (Bcl-2), and factors involved in the mTOR signaling pathway in 30 pulmonary LAM tissues. Immunoreactivity for ER伪, ER尾, progesterone receptor, aromatase, and Bcl-2 was significantly more abundant in epithelioid cells, whereas the status of androgen receptor, 5伪-reductases, and phospho-mTOR signaling was not different in epithelioid and spindle-shaped LAM cells. We further examined the correlation among H scores of these markers using hierarchical clustering analysis. The results indicated that LAM tumors can be further classified into “aromatase” and “mTOR” groups on the basis of the patterns of immunoreactivity, and the 2 types could benefit from different modes of therapy.