IMMUNOHISTOCHEMICAL ANALYSIS OF RETINOIC ACID RECEPTOR-ALPHA IN HUMANBREAST-TUMORS - RETINOIC ACID RECEPTOR-ALPHA EXPRESSION CORRELATES WITH PROLIFERATIVE ACTIVITY

Retinoids are known to prevent mammary carcinogenesis in rodents and i nhibit the growth of human breast cancer cells in vitro. Previously we demonstrated that retinoid inhibition of proliferation of human breas t cancer cell lines is largely mediated by retinoic acid receptor (RAR )-alpha. In this study we describe for the first time the histological distribution of RAR-alpha in 33 breast lesion specimens as determined by immunostaining with RAR-alpha antibody. Nuclear staining was obser ved in tumor tissue and normal portions of the breast samples. Connect ive tissue exhibited relative uniform staining, whereas a wide range o f RAR-alpha expression was found in the epithelial tumor cells. RAR-al pha protein was expressed at significantly higher levels in tumors wit h greater proliferative activity as determined by immunostaining with Ki-67 antibody. This suggests that RAR-alpha expression may be altered with tumor progression. Although a positive correlation between RAR-a lpha mRNA levels and estrogen receptor status of breast tumors has pre viously been documented, we did not find such a relationship at the pr otein level. As RAR-alpha plays a major role in retinoid-mediated grow th inhibition of human breast cancer cells in vitro, our findings sugg est that patients with highly proliferating tumors could be responsive to retinoid therapy independently of their responsiveness to (anti)-e strogens.