Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders

Numerous studies have shown that human breast cancer tissue has the potential to synthesize estrogen through aromatization, which may act as a local growth factor of hormone-dependent cancer cells. This study was performed to localize the site of aromatization in human breast disorders by immunohistochemistry and correlate the findings with steroid receptors, clinicopathological findings, and other steroidogenic enzymes. Specimens from 60 cases of breast disorders, including 33 cases of breast cancer and 27 cases of benign proliferative disorders, were studied immunohistochemically for aromatase. In the carcinoma cases estrogen receptor (ER) and progesterone receptor (PgR) status was determined by enzyme immunoassay and immunohistochemistry, and other steroidogenic enzymes, including P450scc (side-chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and P450c17, were immunolocalized. Aromatase was immunolocalized in interstitial cells and adipocytes as well as other cells in both benign and malignant breast tissues. However, strong immunoreactivity was observed in adipocytes adjacent to carcinoma in all carcinoma cases and in interstitial or stromal cells around carcinomatous glands in 20 carcinoma cases. Intratumoral staining for aromatase did not correlate significantly with age, clinical stage, histopathological type, lymph nodes metastasis, or ER and PgR status. P450scc and 3 beta HSD were focally observed in 18 and 12 cases of carcinoma, respectively, but P450c17 was never observed. Aromatase expression in stromal or interstitial cells, including adipocytes, in breast cancer may be induced by carcinoma cells and locally synthesized estrogens could function as paracrine hormones. Intratumoral aromatase in human breast neoplasms correlated with malignant phenotypes but not with ER status or prognostic parameters, suggesting that other synthetic systems probably generate any biologically significant locally synthesized estrogens in hormone-dependent breast malignancy.