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Estrogen (ER) and progesterone (PgR) receptors were measured simultaneously in 1144 consecutive breast cancer patients to determine the distribution of patients according to receptor and menopausal status when receptor occurrence rates were considered. The prognostic significance of PgR, either alone or in association with ER, was studied on 187 consecutive breast cancer patients treated only by radical mastectomy. All the cases, as regards axillary node status, were pathologically assessed as node negative. These patients did not receive any adjuvant treatment after mastectomy. At 36 months after mastectomy, the follow-up indicated that PgR- patients have a worse prognosis than PgR+ ones. This is evident when PgR alone is considered as a prognostic factor as well as when it is used to identify, within ER+ cases, those with a higher probability of relapse. In conclusion, it can be stated that although PgR status is an independent prognostic factor, it is useful to evaluate ER and PgR simultaneously for better patient management.

Twenty-eight patients with metastatic renal cell carcinoma entered a multicentric prospective study to evaluate the response to high-dose medroxyprogesterone acetate (MPA) and testosterone in MPA failures in relation to sex steroid receptors. No objective remission was seen in the 24 evaluable patients, and only disease stabilizations of short duration were achieved in one-third of treated patients. Stabilizations achieved with second line testosterone were all seen in patients unresponsive to MPA. Receptor studies demonstrated that estrogen, progesterone, or androgen receptors were found in low concentrations and in only 6 of 23 tumors (26%) and 13 normal tissue samples (56%). Surprisingly, no disease stabilization was achieved in patients positive for receptors. It can be concluded that the occasional objective responses to hormone therapy reported in the literature may have been due to some cytotoxic effect of hormone therapy rather than to a true hormonal mechanism.

A membrane purification procedure and an immunoblotting assay have been designed to allow screening of human solid tumors for overexpression of the GP170 glycoprotein without employing a disaggregation method to obtain cell suspensions. The electrophoresed membrane proteins were probed, after Western Blotting, with the C219 monoclonal antibody and iodinated Protein A. The labeling intensity of the bands on the autoradioimmunoblots were quantified by densitometry. To test for the presence of GP170, we used membranes from the UV 2237 fibrosarcoma line and its adriamycin-resistant variant ADMR, grown in vitro or as solid tumor in mice. Membranes of human normal and tumor tissues obtained from previously untreated patients were also tested. An immunoreaction was observed in the adriamycin-resistant UV 2237 lines grown in vitro or in vivo. Quantitatively, the binding of the resistant cell line grown in vitro was higher than that observed in cells grown in mice. Bands in the GP 170 region were observed in 4/7 normal and in 7/7 tumor colon tissues and in the normal medulla from 2 patients with cancer of the renal cortex. No reaction could be found in samples from normal tissue, primary tumor or nodal metastasis from 7 patients with breast cancer.

Estrogen (ER) and progesterone (PgR) receptor content was assayed in 290 premenopausal women with primary breast cancer, in order to investigate the influence of endogenous hormones on cytoplasmic receptor concentrations throughout the menstrual cycle, subdivided into four phases of ovarian function (early and late follicular phase, early and late luteal phase). Of the total population, 231 (79.7%) patients were ER positive and 59 (20.3%) were ER negative; 220 (75.9%) were PgR positive and 70 (24.1%) were PgR negative. The percentages of positive cases were almost constant in each phase. No significant difference in mean values of ER concentration was noted throughout the cycle. Instead, the PgR concentration significantly increased from the first to the third phase (P = 0.02) and decreased from the third to the fourth phase (P = 0.01). Our results suggest that ER- and PgR- cases are homogeneously distributed and not influenced by the phase of the cycle. Moreover, they suggest that PgR measurement in the luteal phase, rather than in other phases, prevents the occurrence of false low PgR levels and, at the same time, improves its prognostic significance and response rate to endocrine therapy.

This article presents results of the first Italian quality control program for determining the estradiol receptor on lypophilized guinea pig and calf uteri. Despite considerable variability in quantitative terms, the results concur in ability to define samples as positive or negative for receptor content. One of the parameters that most strongly influences accuracy of determination of receptor concentration is protein assay. The evaluation of several lyophilized preparations at scalar concentrations permitted identification, by linear regression, for each laboratory of the systematic and non-systematic variables. More comparable results will be forthcoming when a standardized methodology program has been fully adopted.

Estrogen (ER) and progesterone receptors (PgR) appear to be a prerequisite to elicit a biologic response by a hormone-target organ. Current methodologies for analysis of these proteins (e.g., dextran-coated charcoal, DCC) in single-label assay (SLA) require relatively large amounts of tissue material, time and laboriousness. Therefore, we have developed for breast cancer tissue an improved dual-label assay (DLA) for simultaneous titration (by DCC) and/or characterization (by sedimentation properties) of ER and PgR on the same sample, using 125I-E2 and 3H-Org 2058 as tracers. The interaction of 125I-E2 with ER and plasma proteins in comparison to 3H-E2 was studied in terms of specificity, time course, affinity binding and sedimentation pattern. 125I-E2 bound the same molecular forms displayed by 3H-E2 (9 and 3S) but with lower titers (about 1.3-fold), irrespective of the technique used, and did not bind to sex hormone-binding globulin. Simultaneous detection of 125I and 3H was achieved by use of a gamma counter plus a beta counter sequentially. ER and PgR titrations with DCC in DLA were in good agreement with those obtained with SLA, in terms of titers and Ka values. An analogous result was obtained with sucrose density gradient (SDG) analysis. Both the DLA methods were highly reproducible (CV less than 8.0%). Between the rotors available for SDG, the vertical one was preferable because of the larger number of samples processed and of less perturbation of sedimenting receptor molecules. Furthermore, a biochemical application of the method is described. In conclusion, the DLA procedure, by simplifying ER and PgR estimation, makes it possible to study, even on small tumor biopsies, the molecular properties of these proteins in relation to the clinical response of the disease.

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9% of the primary tumors and in 62.4% of the malignant lymph nodes, whereas PgR were present in 73.0% and 50.0% of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6% and 77.1%, respectively. However, 10.4% of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9% had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Twenty-four patients with endometrial carcinoma received tamoxifen (Nolvadex) for 7 days. Before and after administration, circulating hormones (estradiol, testosterone, progesterone, gonadotropins FSH and LH) were evaluated. Estrogen (ER) and progesterone receptors (PgR) in neoplastic tissue were also assayed. Our results show a net increase in PgR content and a significant decrease in gonadotropin levels after the treatment. The authors suggest that clinical trials be conducted using tamoxifen and progestins for adjuvant therapy after surgery of endometrial carcinoma and for the therapeutic approach of advanced carcinoma.

The evaluation of the data is an important step in performing the estrogen receptor test. For this reason an effort has been made to derive a more reliable threshold criteria. Among the parameters considered, Xo, Ka, and BI%, only the former 2 appear to be suitable to allow a proper evaluation of the results. From the analysis of different types of carcinomatous or normal breast specimens, limit values of these parameters have been recovered for positivity and negativity of the estrogen receptor test. We found all the samples showing Ka less than 1.5 x 10(9) M-1 or Xo less than 5 fmol/mg proteins to be negative, those characterized by low values of both the parameters were borderline, and all the remaining ones were positive.