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The role of mineralocorticoids and glucocorticoids under the impact of 11β-hydroxysteroid dehydrogenase in human breast lesions

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Abstract

We attempted to explore the possible involvement of the in situ availability of mineralocorticoids and mineralocorticoid receptor (MR) in the pathogenesis of mammary ductal carcinoma. We also explored their individual profiles among different subtypes of invasive ductal carcinomas of no special type (IDC-NST) by evaluating the status of MR, Glucocorticoid receptor (GR), and 11β hydroxysteroid dehydrogenase (HSD) 1/2 at each stage of the putative cascade of the mammary ductal proliferative disorders. In this study, IDC-NST, ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH), and non-pathological breast tissues were all evaluated by immunohistochemistry. MR was significantly lower in ADH than in DCIS or IDC-NST. 11βHSD2 was significantly lower in ADH than normal breast tissue and 11βHSD1 was significantly higher in DCIS than normal, ADH, or IDC-NST. MR in progesterone receptor (PR)-positive IDC-NST cases tended to be associated with the Ki-67 labeling index. Results of the present study demonstrated that the status of MR and GR in conjunction with the 11βHSDs was correlated with the development of low-grade proliferative disorders in mammary glands. In addition, the potential crosstalk between MR and PR could also influence cell proliferation of breast carcinoma cells but further investigations are required for clarification.

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Abbreviations

ADH:

Atypical ductal hyperplasia

ALDO:

Aldosterone

AR:

Androgen receptor

BC:

Breast cancer

DCIS:

Ductal carcinoma in situ

E2:

Estradiol

ER:

Estrogen receptor

GCs:

Glucocorticoids

GR:

Glucocorticoid receptor

HER2:

Human epidermal growth factor receptor 2

IDC:

Invasive ductal carcinoma

IDC-NST:

Invasive ductal carcinoma of no special type

IHC:

Immunohistochemistry

MG:

Mammary gland

MCs:

Mineralocorticoids

MR:

Mineralocorticoid receptor

PR:

Progesterone receptor

PRB:

Progesterone receptor isoform B

TNBC:

Triple-negative breast cancer

11βHSD:

11Beta-hydroxysteroid dehydrogenases

11βHSD1:

11Beta-hydroxysteroid dehydrogenase type 1

11βHSD2:

11Beta-hydroxysteroid dehydrogenase type2

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Tohoku University School of Medicine, Sendai, Japan

    Mingzhen Cai, Narumi Harada, Minoru Miyashita, Hiroshi Tada & Takanori Ishida

  2. Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Keely McNamara, Yuto Yamazaki & Hironobu Sasano

  3. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-Ku, Sendai, 980-8575, Japan

    Hironobu Sasano

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  1. Mingzhen Cai
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  2. Keely McNamara
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Cai, M., McNamara, K., Yamazaki, Y. et al. The role of mineralocorticoids and glucocorticoids under the impact of 11β-hydroxysteroid dehydrogenase in human breast lesions. Med Mol Morphol 55, 110–122 (2022). https://doi.org/10.1007/s00795-022-00312-1

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