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Biomedical subjects

A Norgren

Publications and source records attributed to A Norgren.

At least 37 records · Page 2Linked to original sources

5-year survival rate in endometrial carcinoma stage I-II related to steroid receptor concentration, degree of differentiation, age and myometrial invasion.

Three hundred and twenty-seven patients with endometrial carcinoma stage I-II were all followed for at least 5 years. The estradiol receptor concentrations were measured in 298 tumors. In 272 cases the progesterone receptor concentrations were measured as well. Both receptors were significant prognostic factors measured as 5 year survival rate. In a Cox regression test stage, degree of differentiation, myometrial invasion and age remained as independent significant factors. Progesterone receptor concentrations were almost significant in a two-sided test including all degrees of differentiation but were significant (p = 0.04) when only poorly differentiated tumors were included. Thus PgR concentrations were used only on poorly differentiated tumors. The patients could be divided into a high risk group (deep myometrial invasion), an intermediate risk group (poorly differentiated carcinomas without deep myometrial invasion but with a low progesterone receptor concentration) and a low risk group (the remaining) with 5 year survival rated of 61%, 80% and 96% respectively.

Adult↗

Spontaneous endometrial hyperplasia. The prognostic significance of steroid receptor concentration. A two year follow-up of patients treated with abrasio only.

The steroid receptor concentrations were measured in 63 patients. The patients were part of a prospective randomized study and were treated with abrasio only. With respect to Cystic Glandular Hyperplasia (43 patients) 16 out of 25 with PgR values less than 10,000 (fmol/mg DNA) were normalized compared to only 4/14 with higher PgR conc (p = 0.03). No limit could be identified regarding patients with Adenomatous Hyperplasia and Atypical Hyperplasia (29 patients). Consequently patients with CGH and a high PgR concentration are recommended for high dose gestagen therapy.

DNA↗

Endometrial hyperplasia: a prospective randomized study of histopathology, tissue steroid receptors and plasma steroids after abrasio, with or without high dose gestagen treatment.

274 patients with spontaneous endometrial hyperplasias were randomized into two groups: one treated with only abrasio, and another with additional 500 mg medroxyprogesterone acetate (MPA) twice weekly for 3 months. Total disappearance of all types of hyperplasias was seen following MPA treatment, whereas with only abrasio about 60% were removed suggesting that MPA does not have to be generally given to eliminate endometrial hyperplasias. Quantitative determinations of tissue steroid receptors and plasma steroids do not seem to be useful for the selection of patients in need of gestagen treatment.

Androstenedione↗

Menopausal status and cut off levels of steroid receptor ligand binding assays in breast cancer.

494 tubuloductal breast carcinomas obtained at operation were assayed for ER and PgR with short-term ligand incubation and isoelectric focusing. Plasma FSH and E2 concentrations available from 156 of the patients showed strictly premenopausal endocrine conditions in patients 45 years or younger; strictly postmenopausal conditions were found at 55 years or older. ER concentrations were significantly lower in biopsies from premenopausal compared with those from postmenopausal patients. ER concentrations assayed in intervening perimenopausal age period were not statistically different from the premenopausal period. An arbitrarily chosen cut off level to differentiate receptor low from receptor high tumours divided premenopausal assays into two equal parts; those from postmenopausal patients were cut at the second lower percentile. Arbitrary cut off levels ignorant of menopausal status should be replaced by fractionation of low and high receptor tumours on a percentile or quartile basis. Clinically, subgroups or subpopulations of patients should be identified with regard to endocrine and/or receptor status and evaluated separately.

Adult↗

Increased recovery of estrogen receptor in crude homogenates of breast cancer biopsies. A preliminary report.

Crude homogenates and cytosols of 31 breast cancer biopsies were analyzed for estrogen receptor, using the ER-EIA monoclonal assay (ABBOTT Laboratories). The recovery of the receptor was significantly higher in all homogenates than in their corresponding cytosols, in six of which the receptor was below the level of detection. The range of the ratio between homogenate and cytosol concentrations was 0.9-8.1 for 25 positive biopsies. If the recent hypothesis of nuclear localization of the receptor is accepted, the values obtained with crude homogenates would more correctly reflect the true concentration of the receptor in the cells.

Biopsy↗

Prognostic value of flow cytometrical DNA measurements in stage I-II endometrial carcinoma: correlations with steroid receptor concentration, tumor myometrial invasion, and degree of differentiation.

The prognostic value of flow cytometric DNA measurements of individual tumor cells was studied in 166 patients with endometrial carcinoma stage I-II. Follow-up time was 1-46 months and 110 patients were followed for more than 2 years. Three different ways of estimating DNA ploidy were evaluated, and the use of normal endometria in defining diploidy was considered the best. DNA-ploidy had a much more marked prognostic value in terms of 2-year recurrence-free survival than other known prognostic parameters, such as degree of differentiation, range of myometrial invasion and estradiol and progesterone receptor concentrations. The proliferative activity as determined by DNA flow cytometrical analysis was not correlated with prognosis.

Aneuploidy↗

Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age.

In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.

Adult↗

Relapse of endometrial carcinoma related to steroid receptor concentration, staging, histologic grading and myometrial invasion.

Estradiol and progesterone receptor concentrations were positively correlated to the stage of the disease and to the grade of the tumors, but not to myometrial invasion. Myometrial invasion of more than the inner third and degree of differentiation are both important prognostic factors. By combining low estradiol receptor concentration and the degree of myometrial invasion in poorly differentiated adenocarcinomas, stage I-II, it was possible to identify a group of patients containing a high percentage of relapses. This group consisted of 60% of all patients with poorly differentiated carcinoma stage I-II, who had a relapse rate of almost 50%, and were thus suitable for aggressive initial treatment.

Adult↗

Observations on wet weight, protein and DNA as reference for steroid receptors in malignant mammary tumours.

Estradiol and progesterone receptors were recorded together with DNA and soluble protein per unit wet weight for 235 breast cancer samples. Receptor concentration values per wet weight showed the greatest range of variation. Receptor expressed per unit wet weight, DNA or protein showed good correlation (rs greater than 0.90). In selected cases different information on receptor concentration levels may be obtained depending on the reference parameter used. An overrepresentation was found of tumours with low receptor concentrations or receptors below the level of detection in a subgroup with a low DNA content, indicating the possibility of false low receptor values in this group. High ER and PgR contents were significantly related to high level of tissue DNA. Low or high content of protein was not associated directly with low or high receptor levels. In this respect DNA is superior to wet weight and protein as reference standards for receptor concentration. Further, DNA offers the additional possibility of a rough correction for non-epithelial components of the tumours. A critical dilution of receptors, as shown by low DNA content in some homogenates, was not apparent but cannot be excluded.

Biopsy↗

Variation of pH of mammary tumour cytosols: potential influence on steroid receptor assay.

Mammary tumour cytosols prepared for steroid receptor assay showed pH values above or below 7.3-7.5 in 50% of the samples. An increase of 0.6 pH units was observed after the addition of dextran coated charcoal. To test the sensitivity of the assay systems to pH changes, breast cancer cytosols were adjusted to pH between 6.0-9.0 before incubation with ligand at 0 degrees C. ER was then separated by isoelectric focusing in a pH gradient between 9.5-3.5 in a routine assay including a dextran coated charcoal step before focusing. PgR was assayed by electrofocusing as well as by a conventional DCC method and Scatchard plot. Unadjusted control cytosols were run in parallel. At pH above or below 7.0-8.0 recovery of receptor was reduced, the loss being most prominent at low pH. At low pH levels Scatchard plots appeared to be of curvo-linear shape. The effect of low intracellular tumour pH on receptor-ligand affinity in vitro may be of great importance as well in vivo, and should be taken into consideration in the therapeutic situation.

Breast Neoplasms↗

Improved method for assay of estradiol and progesterone receptors with special reference to breast cancer.

Isoelectric focusing of estradiol receptor (ER) and multiple point dextran-coated charcoal (DCC) technique for progesterone receptor (PgR) were adapted for assay of both receptors in the same cytosol sample. Technical improvements and increased recovery of receptors were achieved. 1.0 fmol/ml cytosol of ER may be detected; sensitivity of PgR was 5-10 fmol/ml cytosol. Quantitation of ER was made in 414 (95%) out of 434 consecutive breast cancers. Inclusion of isoelectric focusing records showing only qualitative indication for presence of ER resulted in 98% ER containing tumours, supporting the aspect that strictly ER negative tumours are a rarity. Implications for therapy in disseminated disease are discussed.

Animals↗