Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17

Mol Cell Endocrinol. 2016 Feb 15:422:57-63. doi: 10.1016/j.mce.2015.11.014. Epub 2015 Nov 17.

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.

Keywords: Aldosterone-producing adenoma; CYP11B1; CYP11B2; CYP17; Double-immunostaining; Triple-immunostaining.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism*
  • Adrenal Cortex Hormones / biosynthesis
  • Aldosterone / metabolism*
  • Cell Size
  • Cytochrome P-450 CYP11B2 / genetics
  • Cytochrome P-450 CYP11B2 / metabolism*
  • Fluorescent Antibody Technique
  • Humans
  • Hybrid Cells / metabolism
  • Mineralocorticoids / biosynthesis
  • Steroid 11-beta-Hydroxylase / genetics
  • Steroid 11-beta-Hydroxylase / metabolism*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / metabolism*

Substances

  • Adrenal Cortex Hormones
  • Mineralocorticoids
  • Aldosterone
  • Steroid 17-alpha-Hydroxylase
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase