title: Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The presence of hybrid cells indicated the marked intratumoral heterogeneity of steroidogenesis in APAs, particularly in those producing glucocorticoids and mineralocorticoids.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitada
authors.affiliation: 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.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University, Hospital, Sendai, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Morimoto
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Ise
authors.affiliation: Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS, USA; Endocrinology, University of Mississippi Medical Center, MS, USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000450:Aldosterone / Q000378:metabolism*; D048429:Cell Size; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D008901:Mineralocorticoids / Q000096:biosynthesis; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D008901:Mineralocorticoids; D000450:Aldosterone; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase
keywords: Aldosterone-producing adenoma; CYP11B1; CYP11B2; CYP17; Double-immunostaining; Triple-immunostaining