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通过对CYP11B2/B1和CYP17进行密集的双重和三重免疫染色揭示醛固酮瘤中类固醇生成的肿瘤内异质性

Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17.

作者信息

Nakamura Yasuhiro, Kitada Masaaki, Satoh Fumitoshi, Maekawa Takashi, Morimoto Ryo, Yamazaki Yuto, Ise Kazue, Gomez-Sanchez Celso E, Ito Sadayoshi, Arai Yoichi, Dezawa Mari, Sasano Hironobu

机构信息

Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Mol Cell Endocrinol. 2016 Feb 15;422:57-63. doi: 10.1016/j.mce.2015.11.014. Epub 2015 Nov 17.

Abstract

INTRODUCTION

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

The presence of hybrid cells indicated the marked intratumoral heterogeneity of steroidogenesis in APAs, particularly in those producing glucocorticoids and mineralocorticoids.

摘要

引言

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)参与正常人肾上腺皮质醇的合成。然而,它们在醛固酮瘤(APA)中的详细分布仍未完全明确。

材料与方法

我们通过免疫荧光染色和半定量评估,检测了27例APA(双重染色)病例和21例APA(三重染色)病例中CYP11B1/CYP11B2和CYP11B2/CYP17A1的表达情况。

结果

鉴定出共表达CYP11B1/B2(杂交细胞A型)、CYP11B2/17(杂交细胞B型)、CYP11B1/17(杂交细胞C型)和CYP11B1/B2/17(三阳性细胞)的肿瘤细胞。这些细胞的面积和细胞数量相对较少,但三种杂交细胞类型(A/B/C)和三阳性细胞的单个杂交细胞大小不同。

结论

杂交细胞的存在表明APA中类固醇生成存在明显的肿瘤内异质性,尤其是在那些产生糖皮质激素和盐皮质激素的肿瘤中。

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