Henrik Christian Nyholm

Plasma oestrogens in postmenopausal women with endometrial cancer

Objective To study plasma levels of oestrogens and androgens, sex hormone‐binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer.

Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: Correlations with stage and other clinicopathologic features

Abstract OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely ( p p CONCLUSION: The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior.

Expression of epidermal growth factor receptors in human endometrial carcinoma

SummaryLittle data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent at the cell membranes, with a varying pattern in individual carcinomas. EGF-R expression was not correlated with histologie grade, surgical stage, or estrogen/progesterone receptor status evaluated immunohisto-chemically or biochemically in adjacent tissue sections of the tumor. Ten of 13 (77%) atrophic/inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas.

Expression of MIB-1 (paraffin ki-67) and AgNOR morphology in endometrial adenocarcinomas of endometrioid type.

Cell kinetic information is an important adjuvant to histologic grading and to stage in some malignant tumors. Some studies have shown that in endometrial carcinomas, flow cytometric S-phase correlates with known prognostic parameters. In the current study, the expression of silver-stained nucleolar organizer regions (AgNORs) and MIB-1 (ki-67-paraffin) was assessed on paraffin sections in 112 endometrial adenocarcinomas of endometrioid type (EC) (49 hormone users, 63 nonusers). The AgNOR morphology correlated significantly with MIB-1, mitotic count, and nuclear and architectural grade, but not with stage or previous hormone treatment. MIB-1 correlated with all the above parameters except myometrial invasion and stage. Only myometrial invasion and stage correlated with short-term outcome; in such cases tumors from hormone users and nonusers were pooled. The median MIB-1 value was significantly lower in EC from hormone users compared with EC from nonusers; moreover, when tumors from hormone users and nonusers with poor outcome were examined separately, only 29% (four of 14) of the tumors expressed MIB-1 less than the medians in the respective groups, indicating that a prognostic cutoff point may be different in the two groups. Because hormone replacement therapy is very common, this observation has implication for future studies of growth fraction in EC. This is the first study to show that AgNOR morphology is significantly correlated with other markers of growth fraction and histologic grade.

Endometrial adenocarcinoma of endometrioid subtype with squamous differentiation: an immunohistochemical study of MIB-1 (ki-67 paraffin), cathepsin D, and C-erbB-2 protein (p185).

Differences in the immunohistochemical expression of Cathepsin D, C-erbB-2 protein (p185), and growth fraction (MIB-1) in glandular and squamous epithelium in adenocarcinoma of endometrioid subtype were studied together with Cathepsin D in macrophages. The findings were correlated with conventional prognostic parameters. A search for human papilloma virus (HPV) (probes 6/11, 16/18, and 31/33/51) by in situ hybridization was also performed. Formalin-fixed and paraffin-embedded tissues from 61 adenocarcinomas with > 10% squamous epithelium were studied. MIB-1 was very low in squamous epithelium, no correlation was found between MIB-1 in squamous and glandular epithelium, and only the glandular epithelium correlated with depth of invasion and stage, indicating that glands are most important with regard to prognosis. Cathepsin D expression in macrophages was significantly increased in advanced stage and may be of prognostic value, but more studies on tissue sections are needed to evaluate the relationship between its expression in tumor cells and other cells. p185 showed no value as a prognosticator. Finally, our study found HPV infrequently in endometrial carcinomas.

Prolonged dopamine receptor blockade in normoprolactinemic amenorrhea: a double-blind placebo study *

Patients with functional amenorrhea may have a raised central dopaminergic activity, leading to inhibition of pituitary-ovarian function. In a double-blind placebo trial, ten patients with amenorrhea received metoclopramide (MTC) orally in daily doses from 20 to 7.5 mg in a sequential form for 10 weeks. Six patients received placebo. Serum levels for luteinizing hormone (P less than 0.02), follicle-stimulating hormone (P less than 0.05), and prolactin (P less than 0.001) increased significantly during MTC administration, and no (P greater than 0.05) hormonal changes occurred in the placebo group. Six patients observed vaginal bleedings during MTC administration but without postovulatory progesterone levels. Dopamine receptor blockade may activate the hypothalamic-pituitary axis of amenorrheic patients, although an ovulatory response is not achieved.

Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol.

Objective. To study a possible relationship between serum levels of estrogens and androgens and the tumor content of estrogen receptors and progesterone receptors in endometrial cancer.

Decidual prolactin content and secretion at term: Correlations with the clinical data

This study was conducted to describe the distributions of the initial decidual PRL content (D‐PRL) and the decidual PRL secretion (D‐PRL‐s) in vitro at term and to ascertain whether the clinical data might influence these decidual PRL measures and their correlation with the amniotic fluid PRL concentration (A‐PRL). Decidual tissue was obtained after 134 normal pregnancies at term. D‐PRL and D‐PRL‐s into the medium after an 8 h incubation were determined. The distributions of D‐PRL and D‐PRL‐s were skewed to the right. A logarithmic transformation generated symmetric distibutions. Eight women who were delivered by vacuum extraction due to intra‐uterine asphyxia had D‐PRL values similar those in normal vaginal parturition, whereas D‐PRL‐s values were significantly reduced (p < 0.02). No significant difference (p>0.05) was found in the decidual PRL measures in the vaginal deliveries between those receiving labor stimulating medication and those without, or between women who gave birth vaginally and women undergoing elective cesarean section. Stepwise multiple regression analyses of data obtained from 30 women who gave birth after uncomplicated or various pathological pregnancies showed logarithmically transformed A‐PRL to be closely correlated with D‐PRL, and these correlations were improved by including the week of gestation as a second step (p < 0.00001). After normal pregnancy, D‐PRL‐s was significantly correlated with D‐PRL (p < 0.01), and D‐PRL was correlated with the week of gestation (p < 0.05). None of the remaining clinical data improved the correlations. The results indicate that a logarithmic transformation is appropriate when evaluating D‐PRL and D‐PRL‐s at term and that special attention should be paid to the differences in week of gestation and deliveries complicated with intra‐uterine as Dhvxia.

Effect of ouabain and bumetanide on the basal and the osmolality-affected prolactin secretion from human decidual cells in vitro

Human decidual explants were incubated in vitro in media containing 10(-5) mol/l ouabain or 10(-4) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide to change the intracellular ionic concentrations. In isosmotic incubations (osmolality 315 mmol/kg), no significant effect of either 10(-5) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide was found on the decidual prolactin secretion (D-PRL-s). 10(-4) mol/l ouabain significantly decreased both decidual prolactin production and D-PRL-s (P less than 0.05) and was therefore not used for the following cross-over experiments. Hyperosmotic media (387 mmol/kg) were produced by changing the concentration of either sodium chloride, potassium chloride, or mannitol. All increased D-PRL-s compared with the isosmotic media (315 mmol/kg). 10(-5) mol/l ouabain significantly diminished the increase otherwise elicited by the sodium chloride and the mannitol hyperosmotic media. However, in the hyperosmotic potassium chloride medium with 10(-5) mol/l ouabain, the D-PRL-s remained increased. The hyperosmotic medium (252 mmol/kg) reduced D-PRL-s compared with the isosmotic media (315 mmol/kg) and no significant effect of ouabain was found. Bumetanide did not change the D-PRL-s into any of the hypo- or hyperosmotic media compared with the secretion at 315 mmol/kg. Based on experience from other cell types, the results further indicate that the intracellular ionic concentrations could be of importance to the secretion of decidual prolactin in vitro.