DNA synthesis in estrogen receptor-positive human breast cancer takes place preferentially in estrogen receptor-negative cells

Abstract

The primary breast tumors of 27 patients were analyzed for the expression of estrogen receptors (ER) and DNA synthesis. Seventeen tumors were ER-positive, and the simultaneous expression of ER and DNA synthesis could be analyzed in 14 ER-positive tumors. DNA synthesis was measured through the thymidine labeling index (TLI). ER expression was detected by immunohistochemistry with monoclonal antibodies. In these tumors, 38.6% +/- 13.1% of the cells were ER-positive (average TLI = 0.60% +/- 0.70%), as opposed to the presence of 61.4% +/- 13.1% of ER-negative cells (average TLI = 0.65% +/- 0.53%). In 12 of 14 tumors, both ER-positive and ER-negative cells were found to be engaged in DNA synthesis, whereas in two tumors only ER-negative cells were synthesizing DNA. On the basis of the TLI and the proportion of ER-negative and ER-positive cells in the total population, it is suggested that the ER-positive and ER-negative compartments are interrelated in most tumors. In five tumors, the ER-negative compartment would be a precursor of the ER-positive segment, whereas in six tumors the ER-positive segment appears to be a precursor of the ER-negative one. In three tumors, no evidence of an interrelationship between both segments could be found. In the 14 tumors analyzed, it also was found that 69.1% +/- 21.3% of the DNA-synthesizing cells were ER-negative; this probably accounts for the temporary remissions observed after hormonal treatment in breast cancer.

DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer

“…Mitotic frequency analyses (Aaltomaa et al, 1991a) and flow-cytometric analyses (Helin et al, 1989) have shown that the proliferation rate in steroid-receptor-negative tumours is about twice as high as in receptor-positive ones. Moreover, sophisticated analyses indicate that the synthesis of DNA takes preferentially place in steroid-receptor-negative cells in the otherwise receptorpositive tumours (Ballare et aL, 1989). The recent findings by Aaltomaa et al (1991b) showed that proliferation indices as well as classic prognostic factors have only limited predictive value in sex-steroid-receptor-negative tumours, findings which support the above data.…”

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions

“…computer-assisted microscopy) immunohistochemical methods (Cavaliere et al 1996;Charpin et al 1988a, b;Colley et al 1989;Lay®eld et al 1996) has allowed a better characterization of breast cancer heterogeneity in terms of ER + /ER ) and PgR + / PgR ) tumour cell distribution in a given breast cancer. This characterization of tumour heterogeneity can contribute signi®cant information to the determination of the absolute ER/PgR tumour content (Ballare et al 1989(Ballare et al , 1991Cavaliere et al 1996;Charpin et al 1988a, b;Colley et al 1989;Lay®eld et al 1996;Seymour et al 1990). This means that it is now possible to distinguish between a tumour with a large number of ER + cells but with a small quantity of ER per cell and a tumour containing few ER + cells but with a large amount of ER per cell; both are able to produce the same absolute ER value in a biochemical assay.…”