CLINICAL-SIGNIFICANCE OF THE ESTROGEN-REGULATED PS2 PROTEIN IN MAMMARY-TUMORS

A third of breast cancers are estrogen dependent and respond to endocr ine therapy. The estrogen receptor (ER) was the first marker used to p redict the responses to treatment, and two-thirds of ER positive tumor s show a favourable response. Several estrogen-regulated proteins were further studied in a search to enhance the prediction accuracy of ER status: progesterone receptors, 24-K heat shock protein [1], cathepsin D [2], and recently pS2 protein. The pS2 gene, also named BCEI [3], p NR-2 [4], Md2 [5], was first identified by two groups using differenti al screening of a complementary DNA library derived from a human breas t carcinoma cell line (MCF-7) grown with and without estrogens [3,6]. Later on two independent English groups [4,5] and a Japanese group [71 identified a gene similar to pS2. The pS2 mRNA, relatively abundant ( 0.8%) in the MCF-7 cell line when stimulated by estrogens, encodes a c ystein-rich, 84 aminoacids peptide which is secreted by breast cancer cells. The expression of the pS2 gene, pS2 protein assays in tumor cyt osols and more recently pS2 detection by immunocytochemistry, have bee n described in several series of breast cancers [5,8-18].