Mineralocorticoid and glucocorticoid receptors and 11beta-hydroxysteroid dehydrogenases in human breast lesions

概要

Background: Mammary glands are embryologically derived from sweat glands including sebaceous glands and the functional similarity between these two glands has been well known. Both MCs including ALDO and GCs have been reported to influence the functions of sweat glands but their possible involvement of those, especially MCs in the physiology and pathology of mammary glands has remained unknown. Therefore, I immunolocalized MR, GR, 11βHSDs to explore the possible involvement of those above, especially MR in the pathogenesis of mammary glands and their proliferative disorders.

Methods: MR (nucleus and cytoplasm), GR (nucleus), 11βHSD1 (cytoplasm), and 11βHSD2 (cytoplasm) were immunolocalized in 10 normal breast tissues adjacent to a fibroadenoma. MR immunoreactivity was evaluated both in the cytoplasm and nucleus respectively to clarify its significance of the activated status. I also studied mammary ductal proliferative disorders including 35 ADH, 42 DCIS, and 72 IDC cases. In addition, in IDC cases, their correlations with clinicopathological characteristics and the subtypes including luminal A, luminal B, HER2, and Triple-negative breast cancer (TNBC) according to the results of immunohistochemistry of ER, PR, HER2, and Ki-67 were further studied in order to explore their significance in the process of breast tumorigenesis.

Results: Both MR and GR were detected in mammary ductal epithelial cells of normal breasts as well as of the proliferative lesions. MR (both cytoplasm and nucleus) were significantly lower in ADH than DCIS (nucleus: p=0.0131; cytoplasm: p=0.0024) and IDC (nucleus: p=0.0443; cytoplasm: p＜0.0001). GR tended to be higher in IDC than ADH (p＜0.0001) and DCIS (p＜0.0001). 11βHSD2 in ADH was significantly lower than that in normal (p=0.0060) and IDC (p=0.0460); while 11βHSD1 in DCIS was significantly higher than that in normal (p=0.0169), ADH (p<0.0001) and IDC (p=0.0133). MR immunoreactivity (both cytoplasm and nucleus) was significantly correlated with that of PR and tended to be associated with Ki-67 labeling index (cytoplasm: p=0.0622; nucleus: p=0.0620). In addition, GR+/ER+ or GR+/PR+ IDC cases had significantly higher histological grades, compared with those with GR-/ER+ (vs. GR+/ER+: p=0.0343) and GR-/PR+ (vs. GR+/PR+: p=0.0179), respectively and Ki-67 labeling index (GR+/ER+ vs. GR-/ER+: p=0.0191, GR+/PR+ vs. GR-/PR+: p=0.0123).

Conclusion: Results of my present study did indicate that the status of MR and GR in conjunction with the 11βHSDs was correlated with tumor development in human mammary glands. Luminal breast cancer was more sensitive to hormonal steroids than HER2. The potential crosstalk between MR in the cytoplasm and PR could influence cell proliferation of breast carcinoma cells but further investigations are required for clarification.