Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17.
Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17.
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DOI：
10.1016/j.mce.2015.11.014
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发表时间：
2016-02-15
影响因子：
4.1
通讯作者：
Sasano H
中科院分区：
文献类型：
--
作者：
Nakamura Y;Kitada M;Satoh F;Maekawa T;Morimoto R;Yamazaki Y;Ise K;Gomez-Sanchez CE;Ito S;Arai Y;Dezawa M;Sasano H
细胞色素P450 11B2 （CYP11B2）在醛固酮合成中起关键作用，而细胞色素P450 11B1 （CYP11B1）和细胞色素P450 17A1 （CYP17）在正常人肾上腺中参与皮质醇合成。然而，它们在醛固酮产生腺瘤（APA）中的详细分布尚未完全确定。我们采用免疫荧光染色和半定量评价的方法检测了27例APA（双染）和21例APA（三染）中CYP11B1/CYP11B2和CYP11B2/CYP17A1的表达情况。肿瘤细胞共表达CYP11B1/B2 （A型杂交细胞）、CYP11B2/17 （B型杂交细胞）、CYP11B1/17 （C型杂交细胞）和CYP11B1/B2/17（三阳性细胞）。这些细胞的面积和细胞数量相对较小，但三种杂交细胞类型（A/B/C）和三阳性细胞的个体杂交细胞大小不同。杂交细胞的存在表明APAs中类固醇生成的肿瘤内异质性明显，特别是在产生糖皮质激素和矿皮质激素的细胞中。
Cytochrome P450 11B2 (CYP11B2) plays a pivotal role in aldosterone synthesis, while cytochrome P450 11B1 (CYP11B1) and cytochrome P450 17A1 (CYP17) are involved in cortisol synthesis in normal human adrenal glands. However, their detailed distribution in aldosterone-producing adenoma (APA) remains incompletely settled. We examined the status of CYP11B1/CYP11B2 and CYP11B2/CYP17A1 expressions in 27 APA (double staining) cases and 21 APA (triple staining) cases by using immunofluorescence staining and semi-quantitative evaluation. Tumor cells co-expressing CYP11B1/B2 (hybrid cell type A), CYP11B2/17 (hybrid cell type B), CYP11B1/17 (hybrid cell type C), and CYP11B1/B2/17 (triple-positive cell) were identified. The area and cell number of these cells were relatively small, but the size of individual hybrid cells were different between three hybrid cell types (A/B/C) and triple-positive cells. The presence of hybrid cells indicated the marked intratumoral heterogeneity of steroidogenesis in APAs, particularly in those producing glucocorticoids and mineralocorticoids.