Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism
ObjectiveUnilateral primary aldosteronism (PA) includes aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia, and unilateral multiple nodules. The correlation of multiple nodules, especially genotypic and pathological characteristics, remains unknown. KCNJ5 mutation accounts for 60–80...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.823065/full |
| _version_ | 1818669554428018688 |
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| author | Jing Xie Jing Xie Cui Zhang Xuefeng Wang Yiran Jiang Luming Wu Lei Ye Xuan Wang Wen Xie Haimin Xu Weiqing Wang |
| author_facet | Jing Xie Jing Xie Cui Zhang Xuefeng Wang Yiran Jiang Luming Wu Lei Ye Xuan Wang Wen Xie Haimin Xu Weiqing Wang |
| author_sort | Jing Xie |
| collection | DOAJ |
| description | ObjectiveUnilateral primary aldosteronism (PA) includes aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia, and unilateral multiple nodules. The correlation of multiple nodules, especially genotypic and pathological characteristics, remains unknown. KCNJ5 mutation accounts for 60–80% of unilateral PA, so we aimed to explore the correlation of KCNJ5 somatic mutation and CYP11B1/CYP11B2 staining in multiple nodules in unilateral PA.Design and MethodsA total of 56 microdissected nodules from 24 patients with unilateral PA were included. We assessed somatic KCNJ5 mutations, immunohistochemistry for aldosterone synthase (CYP11B2)/cortisol synthase (CYP11B1), and histological cellular composition of nodules together with adjacent adrenal cortical statements.ResultsKCNJ5 mutations were identified in 17 (17/56, 30.4%) nodules from 11 adrenals (11/24, 45.8%). All KCNJ5-mutant nodules were positive for CYP11B2 staining, 6 cases (6/11) had only one KCNJ5-mutant nodular, and the other 5 cases (5/11) had more than one KCNJ5-mutant nodules. Three cases (3/11) had different KCNJ5 mutations in individual nodules. Compared with KCNJ5-positive adrenals, the cortices adjacent to the nodules in KCNJ5-negative adrenals showed significant proliferation (p = 0.004). CYP11B2/CYP11B1 expression patterns revealed great heterogeneity in intensity and range both in KCNJ5-mutant nodules and KCNJ5-WT ones.ConclusionThere is great heterogeneity among nodules from patients with unilateral PA. Countable nodules could be considered as multiple APAs, featuring somatic KCNJ5 mutation, positive CYP11B2 staining, and lack of adjacent cortical proliferation in unilateral multiple nodules. |
| first_indexed | 2024-12-17T06:54:04Z |
| format | Article |
| id | doaj.art-571b371fc342452286786b443c2ec09b |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-17T06:54:04Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-571b371fc342452286786b443c2ec09b2022-12-21T21:59:29ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-04-01910.3389/fmed.2022.823065823065Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary AldosteronismJing Xie0Jing Xie1Cui Zhang2Xuefeng Wang3Yiran Jiang4Luming Wu5Lei Ye6Xuan Wang7Wen Xie8Haimin Xu9Weiqing Wang10Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaObjectiveUnilateral primary aldosteronism (PA) includes aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia, and unilateral multiple nodules. The correlation of multiple nodules, especially genotypic and pathological characteristics, remains unknown. KCNJ5 mutation accounts for 60–80% of unilateral PA, so we aimed to explore the correlation of KCNJ5 somatic mutation and CYP11B1/CYP11B2 staining in multiple nodules in unilateral PA.Design and MethodsA total of 56 microdissected nodules from 24 patients with unilateral PA were included. We assessed somatic KCNJ5 mutations, immunohistochemistry for aldosterone synthase (CYP11B2)/cortisol synthase (CYP11B1), and histological cellular composition of nodules together with adjacent adrenal cortical statements.ResultsKCNJ5 mutations were identified in 17 (17/56, 30.4%) nodules from 11 adrenals (11/24, 45.8%). All KCNJ5-mutant nodules were positive for CYP11B2 staining, 6 cases (6/11) had only one KCNJ5-mutant nodular, and the other 5 cases (5/11) had more than one KCNJ5-mutant nodules. Three cases (3/11) had different KCNJ5 mutations in individual nodules. Compared with KCNJ5-positive adrenals, the cortices adjacent to the nodules in KCNJ5-negative adrenals showed significant proliferation (p = 0.004). CYP11B2/CYP11B1 expression patterns revealed great heterogeneity in intensity and range both in KCNJ5-mutant nodules and KCNJ5-WT ones.ConclusionThere is great heterogeneity among nodules from patients with unilateral PA. Countable nodules could be considered as multiple APAs, featuring somatic KCNJ5 mutation, positive CYP11B2 staining, and lack of adjacent cortical proliferation in unilateral multiple nodules.https://www.frontiersin.org/articles/10.3389/fmed.2022.823065/fullKCNJ5CYP11B2CYP11B1primary aldosteronismunilateral multiple nodules |
| spellingShingle | Jing Xie Jing Xie Cui Zhang Xuefeng Wang Yiran Jiang Luming Wu Lei Ye Xuan Wang Wen Xie Haimin Xu Weiqing Wang Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism Frontiers in Medicine KCNJ5 CYP11B2 CYP11B1 primary aldosteronism unilateral multiple nodules |
| title | Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism |
| title_full | Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism |
| title_fullStr | Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism |
| title_full_unstemmed | Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism |
| title_short | Exploration of KCNJ5 Somatic Mutation and CYP11B1/CYP11B2 Staining in Multiple Nodules in Primary Aldosteronism |
| title_sort | exploration of kcnj5 somatic mutation and cyp11b1 cyp11b2 staining in multiple nodules in primary aldosteronism |
| topic | KCNJ5 CYP11B2 CYP11B1 primary aldosteronism unilateral multiple nodules |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.823065/full |
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