Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism.
Immunohistochemical Analysis of CYP11B2, CYP11B1 and β-catenin Helps Subtyping and Relates With Clinical Characteristics of Unilateral Primary Aldosteronism.
复制标题
CYP11B2、CYP11B1 和 β-连环蛋白的免疫组织化学分析有助于单侧原发性醛固酮增多症的分型并与临床特征相关
DOI：
10.3389/fmolb.2021.751770
复制
发表时间：
2021
影响因子：
5
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Sun L;Jiang Y;Xie J;Zhu H;Wu L;Zhong X;Zhou W;Su T;Wang W
背景：原发性醛固酮增多症是由醛固酮过度生产引起的。虽然常规苏木精-伊红染色可以显示形态异常，但它不能提供任何功能性组织病理学信息。我们的目的是确定细胞色素P11B2、细胞色素P11B1和β-连环蛋白免疫染色在单侧醛固酮增多症中的诊断、功能和预后价值。方法：单侧醛固酮增多症患者134例。应用免疫组织化学技术半定量检测β-连环蛋白、细胞色素P11B2、细胞色素P11B1的表达，并分析其与临床资料的关系。结果：根据细胞色素P11B2染色将患者分为4个亚型：(1)单侧单纯性醛固酮腺瘤(APA)118例，(2)单侧多发性APA 11例，(3)4例醛固酮生成细胞团(APCC)，(4)来源不明1例。调整后的CYP11B2H评分与血清醛固酮、醛固酮/肾素比值(ARR)和血钾相关。在β-连环蛋白染色异常组中，高血压病程、醛固酮、ARR、皮质醇、肿瘤直径、肿瘤面积、细胞色素P11B2H评分均显著高于野生型组。β-连环蛋白染色异常者血钾水平明显降低。临床完全成功组和临床不完全成功组患者的年龄、性别、体重指数、高血压家族史、调整后的细胞色素P11B2和细胞色素P11B1H-记分差异有统计学意义。多因素Logistic回归分析显示，年龄、性别和高血压家族史与完全临床成功独立相关。结论：CYP11B2免疫组织化学染色可提高单侧醛固酮增多症的鉴别诊断。调整后的CYP11B2H评分可作为反映单侧APA严重程度的组织病理学指标。Wnt/β-连环蛋白信号转导异常和β-连环蛋白降解障碍可能促进肿瘤细胞的增殖，增强细胞的类固醇合成能力，提示Wnt通路可能是治疗醛固酮增多症的一个潜在的、可行的治疗靶点。年龄、性别和高血压家族史是单侧醛固酮增多症肾上腺切除术后临床结果的独立预测因素。
Background: Primary aldosteronism is caused by aldosterone overproduction. While conventional hematoxylin-eosin staining can demonstrate morphological abnormality, it cannot provide any functional histopathological information. We aimed to identify the diagnostic, functional and prognostic value of CYP11B2, CYP11B1, and β-catenin immunostaining in unilateral hyperaldosteronism. Method: A total of 134 patients with unilateral hyperaldosteronism were recruited in our study. The expression of CYP11B2, CYP11B1, and β-catenin was evaluated semiquantitatively on 134 patients’ sections using immunohistochemistry technology and the relationship with clinical data was assessed. Results: Patients were classified into four subtypes based on CYP11B2 staining as below: (1)118 patients with unilateral single aldosterone-producing adenoma (APA), (2)11 with unilateral multiple APA, (3)four with aldosterone-producing cell cluster (APCC), and (4)one with an undefined source. Adjusted CYP11B2 H-score was correlated with serum aldosterone, aldosterone to renin ratio (ARR), and serum potassium. In the abnormal β-catenin staining group, hypertension duration, aldosterone, ARR, cortisol, tumor diameter, tumor area, and CYP11B2 H-score were significantly higher than those of the wild-type group. Serum potassium level was significantly lower in the abnormal β-catenin staining group. Age, gender, BMI, family history of hypertension, adjusted CYP11B2 and CYP11B1 H-scores differed significantly between complete clinical success and incomplete clinical success groups. Age, gender and family history of hypertension were independently associated with complete clinical success based on multivariate logistic regression analysis. Conclusion: CYP11B2 immunostaining could improve the differential diagnosis of unilateral hyperaldosteronism. Adjusted CYP11B2 H-score could be used as a histopathological marker to reflect the severity of unilateral APA. Dysregulation of Wnt/β-catenin signaling and impaired β-catenin degradation may provoke the proliferation and enhance the steroidogenic ability of APA tumor cells, indicating that the Wnt pathway might be a potential, actionable, therapeutic target in the treatment of hyperaldosteronism. Age, sex and family history of hypertension were independent predictors of clinical outcome after adrenalectomy for unilateral hyperaldosteronism.