RELATIONSHIPS BETWEEN TAMOXIFEN FINDING PROTEINS IN PRIMARY BREAST-CANCER BIOPSIES

Using high-resolution isoelectric focusing gel electrophoresis (IEF), two tamoxifen binding sites (TBS) with isoelectric point (pI) values o f 4.5 and 4.3 were identified, with different affinities for tamoxifen . The form at pI 4.3 (HTBS) displayed high affinity for the ligand (kD approximate to 5 nM), while the protein at pi 4.5 (LTBS) had lower af finity (kD approximate to 50 nM). LTBS was found in the microsomal fra ction and HTBS in the cytosol. Of a total of 319 tumours studied, 257 were oestrogen receptor (ER) positive and 106 HTBS positive. In this c ombined group, thus able to bind tamoxifen either through the presence of ER or HTBS (or both), ER and PR were both negatively correlated wi th HTBS (P < 0.0001). The oestrogen-induced protein pS2 was assayed in 92 of the 319 tumours, and was also negatively (P < 0.0001) correlate d with HTBS. The levels of HTBS were similar between infiltrating duct al carcinomas without special features (NOS) and non-NOS forms. Howeve r, HTBS concentrations were significantly higher in poorly differentia ted grade 3 carcinomas than grade 2 (P < 0.05) and grade 1 (P < 0.01) forms. Conversely, ER concentration was lower in grade 3 than grade 1 forms (P < 0.05). Both the relationship between high affinity TBS and ER and the high concentration of HTBS in ER-poor grade 3 carcinomas ma y have a bearing on the known variability of tumour response to endocr ine therapy and prognosis.