TY - JOUR
T1 - Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17
AU - Nakamura, Yasuhiro
AU - Kitada, Masaaki
AU - Satoh, Fumitoshi
AU - Maekawa, Takashi
AU - Morimoto, Ryo
AU - Yamazaki, Yuto
AU - Ise, Kazue
AU - Gomez-Sanchez, Celso E.
AU - Ito, Sadayoshi
AU - Arai, Yoichi
AU - Dezawa, Mari
AU - Sasano, Hironobu
N1 - Funding Information:
We thank Mr. Akira Takebe and Ms. Masako Ino (Nikon Instech Co. Ltd., Tokyo, Japan) for their excellent technical advice. Dr. Nakamura is partly supported by the Takeda Science Foundation .
PY - 2016/2/15
Y1 - 2016/2/15
N2 - 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.
AB - 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.
KW - Aldosterone-producing adenoma
KW - CYP11B1
KW - CYP11B2
KW - CYP17
KW - Double-immunostaining
KW - Triple-immunostaining
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U2 - 10.1016/j.mce.2015.11.014
DO - 10.1016/j.mce.2015.11.014
M3 - Article
C2 - 26597777
AN - SCOPUS:84956667088
VL - 422
SP - 57
EP - 63
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
ER -