Estrogen and progesterone receptor assays in human breast cancer: sources of variation between laboratories.

The importance of cytosol preparation as a source of inter-laboratory variation in estrogen (ER) and progesterone (PR) receptor measurements was evaluated together with protein measurements and receptor assays for five laboratories in Sydney, Australia, using pooled, fragmented human breast cancer samples. Protein measurement was only a minor source of variation between the laboratories with a CV of 13%. For ER measurements, sources of variation due to either assay or cytosol preparation methods contributed 40 and 39% CV each. However, the variation due to assay method was reduced to 25% CV when the results from one laboratory with a known effect of a different ER assay protocol were excluded, suggesting that assay standardization could readily reduce this source of variation. In contrast, the source of a large cytosol error (39% CV) could not be identified. Variations in PR results were similar to ER, but the sources could not be accurately estimated. It is concluded that cytosol preparation as well as assay methods were major sources of between laboratory variation and need to be further investigated and standardized. This approach should reduce these sources of variation since it was found that the within laboratory cytosol and assay variations were only 13 and 18% CV, respectively, for the ER measurements.

Relationship between flow cytometric parameters, steroid receptors, and menopausal status in breast cancers.

Of 163 human breast cancers examined, 68% contained detectable aneuploid populations, whilst 32% had apparently normal DNA distributions. A slightly higher incidence of aneuploidy was observed in pre-menopausal patients (83%) than in post-menopausal patients (66%). Also, pre-menopausal patients had slightly higher proportions of S-phase or cycling (S + G2 + M) cells. Estradiol receptor negative (ER-) tumours from post-menopausal patients were found to have the lowest incidence of aneuploidy (59%) and ER- tumours from pre-menopausal patients the highest (91%). There were no significant differences in the proportions of cycling nuclei when receptor status and menopausal status were considered. A weak relationship is shown to exist between flow cytometric data and two common prognostic indicators of breast cancer, namely receptor status and menopausal status.

A pilot study of flutamide. A new agent in the treatment of advanced prostatic cancer.

Flutamide, a new non-steroidal antiandrogenic agent, was administered in the treatment of five assessable patients with advanced carcinoma of the prostate. Two patients showed significant clinical benefit, one showed a reduction in his requirement for analgesia and two failed to benefit; side-effects were minimal. These results indicate the need for a controlled clinical trial of flutamide in patients with prostatic cancer.

Effects of dihydrotestosterone, 17 beta-estradiol and dexamethasone on mitogen--and allogeneic--induced lymphoblastogenesis.

In contrast to the in vivo action of sex steroids the steroidal hormones dihydrotestosterone (DHT) and estradiol (E2) produced a marked variable response on mitogen-induced lymphoblastogenesis. DHT and E2 at concentrations of 10(-11) mol l-1 incubated with mononuclear cell fraction in the presence of mitogens PHA, Con A and PWM caused inhibition, stimulation or no effect. Separation of T and B cell fractions and incubation with DHT and E2 likewise produced variations in response. However, dexamethasone (DEX) strongly inhibited proliferation of all cell fractions, particularly at the higher steroid concentrations. These results suggest that the reported effects of in vivo administered sex hormones on the immune system might possibly be mediated by a precursor cell of peripheral blood mononuclear cells, and that the in vitro system may not be a reproducible test for determining an individual's immunoendocrine status.

Estradiol receptors in subpopulations of breast cancer cells isolated from human primary tumors.

Cancer cells isolated from biopsy specimens from seven women with primary breast cancer were analyzed for estradiol receptors. The cells were separated into subpopulations using the techniques of velocity centrifugation, buoyant density centrifugation, and density gradient electrophoresis. It was found that only large breast cancer cells (with diameters between 10.1-18.5 micrometers) concentrate tritiated estradiol. The total population of cancer cells has diameters between 5.6-18.5 micrometers, and the proportion of large cancer cells from different tumors varies from 8-59% of the total population. It is suggested that clinical regression following endocrine ablation is related to the proportion of large cancer cells and to the concentration of estradiol receptors in these cells.

Human kappa-casein as a tumor marker: purification and properties.

To test the efficacy of kappa-casein as a marker of human malignancy, a protein human milk, ostensibly kappa-casein, has been purified and serum levels determined, by RIA, in normal subjects, breast cancer patients, and lactating women. The results do not support claims by other workers for this protein. Concurrent physicochemical characterization of the protein has shown that it is probably lactoferrin and this result casts some doubt on the earlier studies as it is a major, non-beta component of the casein fraction. It also indicates that caution should be exercised when homology between proteins is used as a guide to identity.

Environmental chemical carcinogenesis.

The methodology of revealing and studying chemical carcinogens in the environment is based on epidemiology, animal testing, and short-term laboratory studies. The techniques and limitations of these respective investigations are described. From evidence of carcinogenicity, extrapolation must be made to assess whether a particular substance is a cause of cancer in humans. This inference depends upon the type of evidence for carcinogenicity. In particular, parameters limiting extrapolation of all laboratory assays include species' specificity and dose response. Control of the environmental distribution of punative carcinogens poses difficulty, both in the selection of substances, and in legislative design. Certain personal habits still constitute the major established carcinogenic hazards for the community-at-large.