Estrogen And Progesterone Receptors Research Articles

Lectin binding patterns of uterine glands in mares with chronic endometrial degeneration.

To evaluate changes of glycoconjugate in uterine glands of endometrial tissues obtained from mares. adult mares. Uterine biopsy samples were collected during the breeding season and analyzed histologically for signs of chronic endometrial degeneration. Stage of the estrous cycle was established, using clinical examination and determination of hormonal status. Uterine tissue samples were analyzed, using lectin histochemical and immunohistochemical techniques (estrogen and progesterone receptors). Connective tissues were stained to determine alterations of ground substance in periglandular fibrosis. Of 50 mares, 30 (60%) were classified as normal or having modest alterations, and 20 (40%) were classified as having moderate or severe endometrial degeneration. In normal equine endometrium, several lectins (Helix pomatia agglutinin, Lotus tetragonolobus agglutinin, Ricinus communis I agglutinin, Ulex europaeus agglutinin, and wheat germ agglutinin) bound to glycoconjugates of the luminal epithelium and openings of uterine glands. Lectin binding patterns of cystic dilated glands or fibrotic glands in endometrial samples were remarkably strong, whereas normal surrounding cells remained unstained. Lotus tetragonolobus lectin was not suitable for detecting endometrial alterations. Connective tissues stained with Alcian blue and results of Hale colloidal-iron binding revealed acidic ground substance in periglandular fibrosis. Estrogen and progesterone receptors were evenly distributed in healthy and affected endometrial samples. Glycoconjugate patterns of uterine glands were altered in mares with chronic endometrial degeneration. Therefore, uterine secretions are likely to be altered. These changes are not induced by changes in content of estrogen and progesterone receptors in endometrial tissues.

Tumor-associated overexpression of the soluble T1-S receptor in lymph node-negative breast cancer.

The oncogene-inducible secreted T1-S glycoprotein is overexpressed in invasive breast carcinomas in mice. As yet, nothing is known about the expression of T1-S in spontaneously occurring human cancers. A report follows on the overexpression of T1-S mRNA in 67% of primary invasive lymph node-negative breast carcinomas (31 of 46 patients) as determined by quantitative reverse transcriptase polymerase chain reaction. Overexpression of T1-S mRNA was independent of the tumor size, the histologic tumor type, and the estrogen-and progesterone-receptor status but was associated with high to moderate differentiation of the tumors (G , G2). T1-S mRNA levels were low to nondetectable in resting normal mammary tissue and benign fibrocystic disease of the breast. Immunohistochemistry confirmed a low to moderate T1 immunoreactivity in epithelial cells of resting mammary tissue and benign fibrocystic disease and highly variable levels of T1 immunoreactivity in breast carcinoma cells. Kaplan-Meier analysis of disease-free survival during a median observation period of 61 months revealed a trend toward a reduced relapse rate and an extended relapse-free survival period for T1-S mRNA--overexpressing breast carcinomas. It is concluded that overexpression of T1-S receptor in lymph node-negative breast cancer may be a potential indicator for tumors with a low metastatic potential.

The shape of age-incidence curves of female breast cancer by hormone-receptor status.

Substantial decline of ovarian hormones at menopause plays an important role in breast cancer etiology. Hormones must bind to specific receptors to elicit biological responses, however. We therefore hypothesized and examined whether the age-specific risk of breast cancer, especially its change at menopause, differs by estrogen and progesterone receptor (ER/PR) status. Age-specific incidence rates, stratified by ER/PR status, were estimated by multiplying the age-specific ER/PR distribution among 3359 cases in the Danish Breast Cancer Cooperative Group by Danish national age-specific incidence rates. International variations in the age-incidence curve were also reviewed in relation to the hypothesis. The incidence of ER +/PR + subtype (62.9% of all cases) increased with age continually, with a sudden decrease in the rate of increase around age 44. The incidence of ER-/PR- subtype (17.6%) increased with age prior to about age 50 but remained unchanged subsequently. The incidence of ER+ /PR- subtype (13.9%) increased rapidly during the menopausal period but only slightly afterwards. The incidence of ER-/PR+ subtype (5.6%) increased until about age 43 and decreased subsequently. The international comparison revealed Western women, particularly the elderly, might be at substantially higher risk for ER+ /PR+ subtype compared to Japanese women. Age-specific risk of breast cancer differs by ER/PR status. The large international variation of breast cancer incidence rates may be explained largely by the risk difference for ER+ /PR+ subtype.

Influence of Fixation, Antibody Clones, and Signal Amplification on Steroid Receptor Analysis

: Various factors influence analysis of steroid receptors, including tissue processing, fixation, and antibody clones used. Furthermore, the detection methods, that is, use of epitope retrieval by microwave heating and signal amplification, may affect the reliability of the results. Eleven different fixation/tissue-processing methods as well as different commercial antibodies for the estrogen-and progesterone-receptors and the tyramine amplification technique were evaluated for optimizing the staining procedures. Moreover, the results from the optimal immunohistochemical procedure were compared with results obtained using a biochemical dextran-coated charcoal assay in 88 breast carcinomas from postmenopausal patients. The four antibody clones tested (1D5, 6F11, 1A6, and antiserum) revealed different sensibility to formalin, either favoring shorter or longer periods of fixation. Overall, a delay in the onset of fixation showed the worst results, whereas overfixation for up to 4 days or pH of formalin had little influence. Using the new tyramine technique it was possible to reduce costs per slide considerably by increasing antibody dilution. Comparison of the biochemical assay with optimized immunohistochemistry in the 88 cases investigated showed an overall concordance of 98.9%. Our study suggests an optimized immunohistochemical procedure that can replace the biochemical “gold standard” if standardization of tissue processing is maintained.

Estrogen Replacement Therapy and Endometrial Hyperplasia

To the Editor. —The PEPI trial group 1 recently demonstrated that in 94% (34/36) of postmenopausal women who developed endometrial hyperplasia in association with estrogen-only replacement, progestin therapy was effective in reversing the hyperplastic changes, while the remaining patients were refractory to progestin therapy. The next natural question that should be considered is whether there are any factors that can reliably predict response to progestin therapy in patients with endometrial hyperplasia. The importance of predicting response to progestin therapy is obvious, considering that the alternative for many patients is hysterectomy. It is reasonable to conjecture that immunohistochemical or molecular markers exist in hyperplastic endometrial tissues, such as estrogen and progesterone receptors (ER/PRs) and proliferative index, which can be exploited to predict response prior to a trial of progestin therapy. In breast cancers, ER/PR status has been shown to reliably predict response to hormonal therapy, and together with a panel of

669 Long term (> 10 years) prognostic value of estrogen and progesterone receptors for operable breast cancer

Estrogen and progesterone receptors (ER-PR) are (questionable) prognostic factors for survival and disease-free survival. We have studied their prognostic value in a long term analysis which included 1203 women operated on for a breast cancer from 1980 to 1985 in a single comprehensive Cancer Centre. The median follow-up is 124 months. Survival curves and metastatic free survival curves were calculated using the Kaplan Meier method. Log-rank test was used to test their differences. A Cox model analysis was performed to evaluate the weight of the different prognostic factors. Overall survival is 64.5% for the whole population. With univariate analysis , nodal involvement was the most predictive value before tumor size, age, SBR grading, progesterone receptors, menopausal status and estrogen receptors. With multivariate analysis , nodal involvement maintains its high prognostic value before PR negativity, age, tumor size and SBR grading for overall survival and before tumor size, SBR grading and PR negativity for metastatic free survival. ER does not have any prognostic significance for survival.

Estrogen and Progesterone Receptor Proteins in Zinc Sulfate, Formalin Fixed Breast Carcinoma: Advantages of a Supersensitive Streptavidin Technique

We report an immunohistochemical method for the assay of estrogen and progesterone receptors (ER/PR) in zinc-sulfate formalin fixed, paraffin embedded tissues of breast carcinomas with Abbott's monoclonal antibodies to ER protein (H222) and PRprotein (JZB39). Small portions of tumor were placed in zinc sulfate formalin, which was then used either as a primary- or a postfixative. Sections were pretreated briefly with trypsin and pronase, and the combination of a supersensitive streptavidin detection system with dilution of the primary monoclonal antibodies yielded an immunoreaction with high nuclear signal and low background. In those instances when only small amounts of breast cancer are available, as is increasingly common, this technique may prove invaluable. (The J Histotechnol 16:51, 1993)

Immunohistochemical analysis of the topographical relationship between the estrogenand progesterone receptor in five human breast cancers

A technique is described which allows precise assessment of the topographical relationship between the estrogen receptor (ER) and the progesterone receptor (PR) in the same histological section. It is based on the analysis of the results of immunohistochemical double staining by computer-assisted image processing. Five human ductal breast cancers were examined. The simultaneous demonstration of both receptors consists in the following principal steps: The primary antisera against the ER (monoclonal rat antibody) and the PR (monoclonal mouse antibody) are incubated simultaneously, but only the anti-ER antibody is demonstrated in the first staining step by using a goat anti-rat antibody as the linking antibody and the PAP complex from the rat, both antisera from the ER-ICA kit. The result is stored as a digitized grey image ("1. object image"). Then the colored end product and the residual peroxidase activity of the PAP complex are removed. In the second staining sequence the anti-PR-antibody is demonstrated by using a rabbit anti-mouse antibody as the linking antibody and the PAP complex from the mouse. The result is exactly positioned and also stored as a digitized grey image ("2. object image"). Though antibodies raised in different species were used, cross-reactivity could not be avoided. Grey values generated by cross-reactivity between the different antibody systems are evaluated in negative controls and are eliminated in the object images. The remaining (specifically stained) structures of both object images are copied into a final image so that the topographical relationship of the ER and the PR becomes obvious. The results show that in the five carcinomas investigated three types of receptor-positive tumour cells can be distinguished: Cells which coexpress the ER and the PR (1), cells which express either the ER (2) or the PR (3). The number of tumour cells showing one of these expression patterns varies from tumour to tumour.

Effect of danazol on estrogen-and progesterone-receptor systems of the human endometrium

Blast cells obtained from the "erythropoietic spleen" of FG-stimulated young mice and cells accumulating in the spleens of preleukemic AKR mice have a marked suppressive effect on spontaneous and mitogen-induced proliferation of young mouse splenocytes in vitro and suppress the development of humoral immune response in immunized recipients during syngeneic transfer in vivo. Some disturbances in erythron system in preleukemic AKR mice manifested in the accumulation of immature erythroid precursors which are suppressors of immunocompetent lymphocytes are suggested to be a pathogenetic link in the development of leukemia.

Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients.

Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.