Localization of mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase type II in human breast and its disorders.

Mineralocorticoid receptors have been detected in the normal human breast and breast cancers. The expression of mineralocorticoid receptor (MR) and llbeta-hydroJysteroid dehydrogenase type II (11sHSD2), which confers specificity on MR for aldosterone, was examined by immunohistochemistry in 114 samples from normal human breast and benign and malignant breast lesions in order to study its possible biological significance. MR and llsHSD2 were immunolocalized in the ductal epithelium in 39/40 (98 %) and 36/40 cases (90%) of normal breast, 21/22 (95%) and 15/22 cases (68%) of fibrocystic changes, and 11/11 (100 %) and 8/11 (73%) cases of fibroadenoma, respectively. Cases positive for 11 sHSD2 also expressed MR but the patterns of expression varied greatly among examples of normal breast and benign breast diseases. There was a significant correlation between labeling indices of MR and 11sHSD2 in normal breast (p<0.01) and in benign breast disease (fibrocystic change (p<0.05) and fibroadenoma (p<0.05)). In invasive carcinomas, immunoreactivity for MR and 11sHSD2 was detected in malignant cells in 32/41(78%) and 16/41(39%) cases. Both MR and 11sHSD2 labeling indices were significantly higher in invasive ductal carcinoma (22 cases) than invasive lobular carcinoma (19 cases) (p<0.01). There was a significant correlation between labeling indices of MR and 11sHSD2 when analyzing all infiltrating carcinomas (p<0.01), but not when assessing invasive lobular or invasive ductal carcinomas separately. These results indicate that the 11 sHSD2 enzyme generally colocalizes with the MR in the ductal epithelial cells of human breast, which may allow aldosterone to occupy its physiological receptor, and the expression of MR and llsHSD2 appears to be related to ductal differentiation of breast carcinomas.