Uchida Toyoyoshi, Nishimoto Koshiro, Fukumura Yuki, Asahina Miki, Goto Hiromasa, Kawano Yui, Shimizu Fumitaka, Tsujimura Akira, Seki Tsugio, Mukai Kuniaki, Kabe Yasuaki, Suematsu Makoto, Gomez-Sanchez Celso E, Yao Takashi, Horie Shigeo, Watada Hirotaka
Departments of Metabolism & Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Uro-Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.
Endocr Pathol. 2017 Mar;28(1):27-35. doi: 10.1007/s12022-016-9441-8.
Most adrenocortical carcinomas (ACCs) produce excessive amounts of steroid hormones including aldosterone, cortisol, and steroid precursors. However, aldosterone- and cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary aldosteronism and subclinical Cushing's syndrome. Removal of the tumor cured both conditions. In order to examine the expression patterns of the steroidogenic enzymes responsible for adrenocortical hormone production, 10 tumor portions were immunohistochemically analyzed for aldosterone synthase (CYP11B2), 11β-hydroxylase (CYP11B1, cortisol-synthesizing enzyme), 3β-hydroxysteroid dehydrogenase (3βHSD, upstream enzyme for both CYP11B2 and CYP11B1), and 17α-hydroxylase/C17-20 lyase (CYP17, upstream enzyme for CYP11B1, but not for CYP11B1). CYP11B2, CYP11B1, and 3βHSD were expressed sporadically, and their expression patterns varied significantly among the different tumor portions examined. The expression of these enzymes was random and not associated with each other. CYP17 was expressed throughout the tumor, even in CYP11B2-positive cells. Small tumor cell populations were aldosterone- or cortisol-producing cells, as judged by 3βHSD coinciding with either CYP11B2 or CYP11B1, respectively. These results suggest that the tumor produced limited amounts of aldosterone and cortisol due to the lack of the coordinated expression of steroidogenic enzymes, which led to mild clinical expression in this case. We delineated the expression patterns of steroidogenic enzymes in ACC. The coordinated expression of steroidogenic enzymes in normal and adenoma cells was disturbed in ACC cells, resulting in the inefficient production of steroid hormones in relation to the large tumor volume.
大多数肾上腺皮质癌（ACC）会产生过量的类固醇激素，包括醛固酮、皮质醇和类固醇前体。然而，ACC中产生醛固酮和皮质醇的细胞尚未有免疫组化方面的描述。我们报告1例导致轻度原发性醛固酮增多症和亚临床库欣综合征的ACC病例。切除肿瘤治愈了这两种病症。为了检测负责肾上腺皮质激素生成的类固醇生成酶的表达模式，对10个肿瘤组织进行了醛固酮合酶（CYP11B2）、11β-羟化酶（CYP11B1，皮质醇合成酶）、3β-羟类固醇脱氢酶（3βHSD，CYP11B2和CYP11B1的上游酶）以及17α-羟化酶/C17-20裂解酶（CYP17，CYP11B1的上游酶，但不是CYP11B2的上游酶）的免疫组化分析。CYP11B2、CYP11B1和3βHSD呈散在表达，且在所检测的不同肿瘤组织中其表达模式差异显著。这些酶的表达是随机的，且彼此不相关。CYP17在整个肿瘤中均有表达，甚至在CYP11B2阳性细胞中也有表达。根据3βHSD分别与CYP11B2或CYP11B1共定位判断，小部分肿瘤细胞群体为产生醛固酮或皮质醇的细胞。这些结果表明，由于类固醇生成酶缺乏协同表达，该肿瘤产生的醛固酮和皮质醇量有限，这导致了本病例中的轻度临床表现。我们描绘了ACC中类固醇生成酶的表达模式。ACC细胞中正常细胞和腺瘤细胞类固醇生成酶的协同表达受到干扰，导致相对于大肿瘤体积而言类固醇激素产生效率低下。
