Yasuhiro Nakamura1, Masaaki Kitada2, Fumitoshi Satoh3, Takashi Maekawa4, Ryo Morimoto5, Yuto Yamazaki4, Kazue Ise4, Celso E Gomez-Sanchez6, Sadayoshi Ito7, Yoichi Arai8, Mari Dezawa2, Hironobu Sasano4. 1. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp. 2. Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan. 3. Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University, Hospital, Sendai, Japan. 4. Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. 5. Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University, Hospital, Sendai, Japan. 6. Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS, USA; Endocrinology, University of Mississippi Medical Center, MS, USA. 7. Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan. 8. Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
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.
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.
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