Expression of 5α-reductase type 1 in breast cancer and adjacent non-malignant tissue: an immunohistochemical study

Intratumoral biosynthesis of sex steroids is thought to play a role in the pathogenesis and development of human breast cancer. There is evidence that androgens can inhibit the development and progression of breast cancer. Among the enzymes involved in the biosynthesis of androgens, 5α-reductase plays a key role by reducing testosterone to dihydrotestosterone, the most potent androgen. Two isoforms of 5α-reductase have been characterized and 5α-reductase type 1 is predominant in breast cancer tissue. We developed specific antibodies to 5α-reductase type 1 and studied the expression of the enzyme in 84 specimens of breast carcinoma and adjacent non-malignant tissues by immunohistochemistry. The results were correlated with the expression of androgen receptor, estrogen receptor α, progesterone receptor and CDC47, a cell division marker as well as the tumor stage, tumor size, nodal status and menopausal status. The expression of 5α-reductase type 1 in 61% of breast cancer specimens appeared significantly lower than that observed in normal adjacent tissues (87% of cases being positive). There was no significant correlation between 5α-reductase type 1 expression and the clinicopathological parameters studied. The decrease in 5α-reductase type 1 expression in breast cancer as compared to that observed in the adjacent normal tissues could play a role in the development and/or progression of the cancer by modifying the intratumoral levels of androgens.