ESTROGEN-RECEPTOR ISOFORMS, THEIR DISTRIBUTION AND RELATION TO PROGESTERONE-RECEPTOR LEVELS IN BREAST-CANCER SAMPLES

Oestrogen receptors (ER) in breast cancer tumours are highly heterogeneous. In this study, the variability in the profile of ER isoforms and its relation to progesterone receptor (PgR) levels in breast tumours has been studied. Using high resolution isoelectric focusing (IEF) 4 ER isoforms can be detected with pI values of 6.1 (corresponding to the 8S ER), and 6.3, 6.6 and 6.8 (all of which have a sedimentation coefficient of approximately 4S in sucrose density gradients). Data were obtained on the soluble receptors from supernatants of 66 ER-positive primary breast tumour homogenates using high resolution IEF. In 43 of these samples PgR levels were also measured. The isoform at pI 6.6 was present in 97.0% of tumours, the isoform at pI 6.1 in 83.3%, the pI 6.3 isoform 39.4% of tumours and the pI 6.8 isoform in only 33.3% of tumours. Only 12.1% of tumours studied contained the full complement of ER isoforms (pl 6.1, 6.3, 6.6 & 6.8). The ER isoforms at pI 6.1 & 6.8 were only found in PgR-positive (> 10 fmol PgR/mg protein) tumours. Some tumours contained only a single ER isoform at pI 6.6 or 6.1, but those at pI 6.3 and 6.8 were never found singly. Tumours containing 3 or 4 ER isoforms had significantly higher levels of PgR (> 90 fmol/mg protein) than those with only 1 or 2 (P<0.001). The presence of ER isoforms at pl 6.3 and pl 6.8 also significantly correlated with high levels of PgR (P<0.001). This variability in the ER isoform profile of breast tumours and their correlation with PgR levels may have a bearing on prognosis and tumour response to endocrine therapy.