Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium

Abstract

Summary In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental al., 1993) and those apparently cured of their endometrial cancer, who yet wish to receive the benefits of hormone replacement therapy (Creasman et al., 1991).Placental protein 14 (PP14) (Bolton et al., 1983) is one of the major proteins secreted by the normal endometrium and the decidua in early pregnancy (Bell et al., 1985;Julkunen et al., 1985). Placental alkaline phosphatase (PLAP), an isoenzyme of the alkaline phosphatase group (Fishman et al., 1968), originally isolated from human trophoblast, is also expressed in other non-malignant human tissues (Goldstein et al., 1982;McLaughlin et al., 1984). PLAP is found to be elevated in the sera of some patients with cancers, particularly those of the reproductive tract (Nathanson & Fishman 1971;Wahren et al., 1979). The beta subunit of human chorionic gonadotrophin (P-hCG), a normal product of the trophoblast, and CA-125 (Bast et al., 1981) are both wellcharacterised oncofetal antigens (Braunstein, 1983) found to be synthesised by many normal tissues and epithelial carcinomas of the reproductive tract.We have established an in vitro system for the culture of normal and malignant endometrial epithelium. The differential expression of markers has been characterised in frozen tissue sections, primary cell cultures and in an established endometrial cell line, in order to demonstrate their specific production by the cancers as a preliminary to evaluating their use as clinical markers. Materials and methods TissuesSamples of human endometrium were obtained during normal non-conceptional menstrual cycles from women undergoing diagnostic curettage for gynaecological investigations. In the premenopausal tissues the phase of the menstrual cycle was determined from the last menstrual period and conCorrespondence: C.J. Gallagher. Received 15 October 1993; and in revised form 24 January 1994.firmed by histology as being proliferative (n = 10), secretory (n = 11) or mid-cycle (n = 10). The endometrium was normal by histological examination, and no other gynaecological abnormality was present except in three cases of endometriosis and two of cervical carcinoma in situ (CIN III). Five samples of perimenopausal endometrium with weak proliferative activity (n = 4) or inactive under hormone replacement therapy (n = 1) were obtained from hysterectomies for fibroids (n = 4) or CIN III (n = 1). Samples from postmenopausal women were also obtained from patients undergoing hysteroscopy or hysterectomy; two of these were atrophic, two showed simple hyperplasia and 17 were histologically diagnosed as well-differentiated endometrial adenocarcinoma. None of these...

Angiogenic role for glycodelin in tumorigenesis

“…There is speculation that glycodelin may modulate the reaction of the immune system of the patient toward the malignant tumor (28). Both our findings (20) and those of others (14,29) have demonstrated that glycodelin expression is increased in tumor tissues. Glycodelin is expressed mainly in tumor cells and endothelial cells of small blood vessels nearby, which could suggest that the presence of glycodelin might be related to neovascularization in tumor tissues.…”

Glycodelin in reproductive endocrinology and hormone-related cancer

“…The basement membrane plays an important part in stromal-epithelial interactions. Whereas glycodelin is a major bioactive protein in the normal secretory endometrium, it has not been detected in endometrial adenocarcinoma tissue (112). But, glycodelin can be induced in endometrial adenocarcinoma cells.…”

HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium

“…Patch-clamp recordings were performed on primary cell cultures obtained from endometrial adenocarcinoma samples, essentially according to Chatzaki et al (1994). Briefly, hysterectomy specimens were first trimmed and minced, then dissociated through a first digestion with collagenase II (Roche, 0.05 mg ml Ϫ1 final concentration) at 37˚C for 2 hours, and a second treatment with trypsin/EDTA solution (0.5 g ml Ϫ1 trypsin, 0.2 g ml Ϫ1 tetrasodium EDTA, Sigma) for 10 min at room temperature with constant agitation.…”