Production of fibronectin by peritoneal macrophages and concentration of fibronectin in peritoneal fluid from patients with or without endometriosis.

Fibronectin, a known growth factor for fibroblasts, is produced by alveolar macrophages from patients with interstitial pulmonary fibrosis. Because peritoneal macrophages have been implicated in the disease process of endometriosis, we measured the production of fibronectin by peritoneal macrophages in vitro and the concentration of fibronectin in peritoneal fluid samples. Twenty-nine patients had a normal pelvis, 22 had endometriosis, and 14 had tubal occlusion and/or adhesions. Human peritoneal macrophages demonstrated de novo synthesis of fibronectin. The peritoneal macrophage fibronectin was detected by an enzyme-linked immunosorbent assay for serum fibronectin. Peritoneal macrophages from patients with endometriosis produced approximately three times the amount of fibronectin as normal patients or patients with tubal occlusion and/or adhesions (P less than or equal to .01 and P less than or equal to .02, respectively). The mean peritoneal fluid concentration of fibronectin, however, was about 30% lower in patients with endometriosis than in normal patients (P less than or equal to .02). We suggest that increased peritoneal macrophage fibronectin production in patients with endometriosis may contribute to the adhesion formation and associated reactive fibrosis seen in this disease, and may also influence the implantation of endometrial cells and their subsequent growth in the pelvis.

The prognostic importance of steroid receptors in endometrial carcinoma.

Three hundred forty-nine cases of primary endometrial carcinoma (endometrioid, adenosquamous, and clear-cell) were studied to investigate the relative prognostic importance of age, menopausal status, stage, histology, myometrial invasion, and estrogen and progesterone receptor content. Excluding menopausal status, all of these variables had a significant relationship to overall survival in a univariate analysis. Using a Cox multivariate regression analysis, stage, age, and an estrogen receptor value of more than 70 fmol/mg protein, combined with a progesterone receptor value of more than 30 fmol/mg protein, were independently associated with survival. The results demonstrate that for maximum prognostic information, both estrogen and progesterone content of tumors should be measured. Maximum prognostic information is obtained by using cutoff levels that are much higher than those traditionally accepted. This has particular relevance for patient stratification in clinical trials investigating receptor information and response to adjuvant or therapeutic treatment.

Protein, progesterone, and protease inhibitors in uterine and peritoneal fluids of women with endometriosis.

This study was undertaken to determine whether women with endometriosis have altered protein, progesterone (P), and protease inhibitor concentrations in their uterine fluid and peritoneal fluid (PF) compared with controls at different phases of the menstrual cycle. Uterine flushings (UFs), PF, and blood were obtained during the follicular and luteal phases of the cycle from 29 normal women and 16 women who were diagnosed as having endometriosis. Protein content in UF did not change significantly throughout the cycle in either group. However, PF protein in patients with endometriosis was significantly (P less than 0.05) higher than in controls during the luteal phase. Total UF P was significantly (P less than 0.05) reduced in women with endometriosis during the late luteal phase. During the early luteal phase, trypsin inhibitory activity in UF from normal women was significantly (P less than 0.05) higher than at any other phase of the cycle, whereas inhibitory activity in UF from patients with endometriosis remained relatively constant. Patients with endometriosis had significantly (P less than 0.05) higher total activity in PF during the early luteal phase than did controls. These results indicate that women suffering from endometriosis have significantly lower levels of P and less protease inhibitor within their uterine cavity during the luteal phase of the cycle, and significantly higher concentrations of protein and protease inhibitor in PF during the luteal phase.

Peritoneal fluid environment and infertility.

The PF environment is one that hosts the processes of ovulation, gamete transportation, fertilization, and early embryonic development. The cellular and acellular constituents of this dynamic fluid are in a constant interactive state, being influenced by the physiologic events of the menstrual cycle and pelvic disease processes; these constituents probably influence disease manifestation and reproduction. The importance of understanding this zone of early reproductive life has been now recognized. We hope that future investigations will define the exact role(s) of known components and some yet-to-be defined substances of PF in disease processes that affect reproductive function. With better understanding of normal and abnormal events in this pelvic microenvironment, we can develop rationales for novel treatment modalities.

Hormonal activity of epithelial ovarian tumours in post-menopausal women.

Concentrations of progesterone and oestradiol in peripheral serum and tumour cyst fluid were measured in 42 post-menopausal women with epithelial ovarian tumours (17 cancer, 6 borderline malignant, 19 benign tumours) and in 19 post-menopausal women without ovarian neoplasms. The hormonal response of the endometrium was assessed, progestogen and oestrogen receptor content in the tumour tissue case recorded, and tumour deoxyribonucleic acid (DNA) ploidy was measured by flow cytometry. No significant differences were found between the mean serum steroid levels in patients with malignant, borderline or benign tumours, but the mean serum levels of oestradiol in patients with malignant or benign ovarian tumours were higher than those in the controls. Endometrial hormonal activity was seen in 19% of the samples studied. Malignant and benign mucinous epithelial tumours were the types most frequently associated with hormonal activity. Increased levels of sex steroids were seen in the cyst fluid of serous malignant and borderline malignant tumours, while benign tumours were inactive. The steroid receptor content of the various tumour types did not vary significantly. Ten (59%) out of 17 ovarian carcinomas were found to be aneuploid and 41% diploid as measured by flow cytometry. No significant differences in serum levels of progesterone and oestradiol were found between aneuploid and diploid ovarian carcinomas. These results contribute to our knowledge of the hormonal activity of epithelial ovarian tumours in post-menopausal women.

The potential value of imprint cytology in cytochemical localization of steroid hormone receptors in ovarian cancer.

Steroid hormone receptors were studied in 45 patients with primary, recurrent, or metastatic ovarian cancer in cryostat-frozen sections and imprint preparations. The ligands, 17 B-estradiol-6-carboxymethyloxine-bovine serum albumin fluorescein isothiocyanate (FITC-BSA estradiol) and hydroxyprogesteronehemisuccinate bovine serum albumin tetramethylrhodamine isothiocyanate (TMRITC-BSA progesterone) were used in the fluorescent cytochemical method. Results were compared with standard dextran-coated charcoal (DCC) biochemical assay. An overall significant correlation between biochemical values and cytochemical results was found. However, the imprint results were more sensitive and more specific than the frozen section results. A statistically significant difference (P less than 0.05) was observed between touch preparation material and frozen section specimens by the fluorescent method.

Peritoneal endometriosis. Report of a case with cytologic, cytochemical and histopathologic study.

The cytologic and histochemical data in a case of extensive peritoneal endometriosis are presented. The presence of macrophages heavily laden with blue and dark pigment (as demonstrated by May-Grünwald-Giemsa, Perls and Fontana stains) and scattered non-neoplastic endometrial cells in hemorrhagic ascitic fluid indicated a diagnosis of peritoneal endometriosis. Metabolized hemoglobin material was related to both recent and older hemorrhages.

The cytokeratin profiles of ovarian common "epithelial" tumors.

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

[Electron spin resonance study of the structure of the spin glass type in nodular variant of adenomyosis]. / Issledovanie metodom EPR struktury tipa spinovykh stekol v tkaniakh uzlovatoi formy adenomioza.

Wide ESR signals with g-factor 2.10 (B = 23 mT) and g = 3.0 (B = 80-120 mT) were recorded in the tissues of the nodular form of adenomyosis of women's uterus at the temperature range 20-300 K. The intensity maxima of these signals were at 150 +/- 20 K.

[Intracellular distribution of estrogen receptors in the human endometrium]. / Vnutrikletochnoe raspredelenie éstrogennykh retseptorov v éndometrii cheloveka.

Fifty samples of endometrial tissue from healthy women with regular menstrual cycle and from patients with uterine myoma, ovarian cystoma, uterine hypoplasia and endometriosis were studied. The amount of cytoplasmic (total and free) and nuclear estradiol-binding sites as well as estradiol (E2) concentration in the endometrial cells were estimated. Level of E2 in the peripheral blood plasma did not correlate with its content in endometrial cells. At the same time, amount of cytoplasmic estrogen receptors bound with E2 did not correlate with the estradiol content in cytoplasm. The data obtained suggest the leading role of the cytoplasmic estrogen-receptors interaction in development of hormonal effect on the tissue. The formation of hormone-receptor complexes appears to be controlled by some additional factors of unknown nature.

Estrogen and progesterone cytosol receptor concentration in endometriotic tissue and intrauterine endometrium.

Cytosol estrogen (ER) and progesterone (PR) receptors were assayed in peritoneal and ovarian endometriotic tissue from 20 patients. In 12 of the cases the intrauterine endometrium was assayed as well. The control material consisted of normal endometrium from 30 women. The receptor content of the endometriotic tissue was less than that of the endometrium of the same patient. In most cases no receptors could be detected (12/20 cases ER-, 7/9 cases PR-) irrespective of the phase of the menstrual cycle. The endometrial receptor concentrations were that same in patients with endometriosis as in the control group. There were no differences in binding characteristics of the receptors in the two tissue types. It is concluded that endometriotic tissue contains lower a concentration of cytoplasmic ER and PR than the normal endometrium.

Altered progesterone/estrogen receptor ratios in endometriosis. A comparative study of steroid receptors and morphology in endometriosis and endometrium.

In a comparative study of endometriosis and endometrium, specimens were taken from both endometriotic and endometrial tissue in 14 patients. Receptor assays and histological examinations were performed on both specimens. Cytosolic estrogen receptors (ERc) as well as cytosolic progesterone receptors (PRc) were detected in 9/14 and 12/12 cases of endometriosis respectively. Nuclear estrogen receptors (ERn) were detected in 4/4 cases of endometriosis. Expressed as fmol/mg cytosol protein, significantly higher values of both ERc and PRc were found in endometrium than endometriosis (p less than 0.01). However, when the ratio between PRc and ERc was considered, significantly higher PRc/ERc ratios were found in the cytosol of endometriotic tissue (p less than 0.01). Thus the lower receptor concentrations found in endometriosis cannot be explained solely as ectopic endometrium being diluted by nonreceptor-containing tissue. In spite of high PRc/ERc ratios in endometriosis, secretory changes similar to those found in endometrium were observed in only one of 7 cases (p less than 0.05).

Comparison of cytosol estrogen and progestin receptor status in malignant and benign tumors and tumor-like lesions of human ovary.

PIP: In an effort to gather more information regarding the human ovarian malignancies that respond favorably to hormone therapy, estrogen (ER) and progestin (PR) receptors in 21 malignant ovarian tumors were measured. The findings were compared with those in 29 benign tumors and 28 tumor-like ovarian lesions. Marked differences in steroid receptor distributions were observed between the 3 groups. Only 38% of the malignant tumors simultaneously contained measurable amounts of both receptors. The corresponding figure for the benign tumors was 76%. The malignant tumors were more frequently (29%) receptor-negative than the benign tumors (7%). The major difference in the tumor-like lesions was the high frequency (43%) of samples containing PR only, as compared with the other 2 groups. The respective concentrations of ER and PR were 114 + or - 42 and 148 + or 76 (malignant tumors), 71 + or - 34 and 132 + or - 32 (benign tumors), and 19 + or - 16 and 251 + or - 88 (tumor-like lesions). Of the malignant tumors, endometrioid carcinoma was characterized by a relatively high mean PR content. In undifferentiated carcinoma a high ER content was associated with a low PR concentration. Steroid receptor content was very similar in benign epithelial tumors with different histological properties.^ieng

[Comparative studies on the value of acute phase proteins and CA-125 for monitoring patients with ovarian cancer]. / Vergleichende Untersuchungen über die Wertigkeit von Akute-Phase-Proteinen und CA-125 für das Monitoring von Patientinnen mit Ovarialkarzinom.

In a study of 71 patients with malignant ovarian tumors serum levels of CA-125, C-reactive protein (CRP), alpha-1-antitrypsin and coeruloplasmin were analysed. In contrast to the tumor-free group significantly higher values of CA-125, CRP and alpha-1-antitrypsin were found in the group with recurrent disease. However, the serum-concentrations of coeruloplasmin remained unchanged in both groups. In the group with progressive disease the median values of CA-125 were greater than 65 U/ml and of CRP greater than 12 micron/ml, respectively. The median serum concentrations of alpha-1-antitrypsin (2 to 4 mg/ml) and coeruloplasmin (150 to 600 ng/ml) did not reach their cut-off levels. Beside CA-125 the analysis of CRP and alpha-1-antitrypsin is an additional helpful procedure for the monitoring of patients with malignant ovarian tumors.

The simultaneous expression of human chorionic gonadotropin and carcinoembryonic antigen in the female genital tract. Localization by immunocytochemistry.

Tissue from 180 gynecologic disorders were studied for the simultaneous expression of HCG and CEA, utilizing the immunoperoxidase technique. Of the total population, 0.5% expressed both antigens, 8.8% expressed only hCG, and 5.5% expressed only CEA; 85% expressed neither. The greatest variability of marker expression was among the ovarian and endometrial neoplasms.

Estrogen and progestin receptors in endometriosis lesions: comparison with endometrial tissue.

Cytosol estrogen (ER) and progestin (PR) receptors were quantified in 47 endometriosis lesions from 41 patients and compared with receptor measurements in the endometrial tissue of nine of these patients. Half of the specimens of endometriosis tissue contained PR only, in concentrations that were significantly lower than in the endometrium. Only 30% of the specimens of endometriosis tissue contained the two receptors simultaneously, and levels of ER were very low compared with those in the endometrium. Levels of PR in the specimens of endometriosis tissue were highest at the periovulatory period, whereas concentrations of ER tended to be highest at the beginning and close to the end of the cycle. These results suggest that regulation of these receptors is dissimilar in endometriosis lesions and endometrium. It remains to be seen whether differences in receptor distribution in the lesions of individual patients could explain differences in the course of this disease, and have therapeutic implications. The presence of PR in the majority of the endometriosis lesions is in accord with the favorable therapeutic response often obtained with progestin treatment of this disease.