concanavalin-a and Endometrial-Hyperplasia

Lectins are proteins and glycoproteins of non-immune origin which bind specifically to carbohydrate residues, agglutinate cells and/or precipitate complex carbohydrates. Lectin-binding patterns in normal, hyperplastic and neoplastic endometria were studied using four biotinylated lectins (Con A, LCA, e-PHA, l-PHA) and the avidin-biotin-peroxidase technique. Canavalia ensiformis agglutinin (ConA) and Lens culinaris agglutinin (LCA) reacted strongly with the luminal borders and the cytoplasm of epithelial cells but, whilst in normal and benign endometrial tissues the cytoplasmic staining was confined to the apical and the basal aspect of the cells, in endometrial carcinomas and in some atypical hyperplasias lectin binding also occurred in the lateral cytoplasm (Con-A-lat), although in differing proportions of cells. Interestingly, extensive Con-A-lat in the tumour cells was much more frequent in non-endometrioid carcinomas (P<0.05) and was significantly associated with poor histological differentiation (P<0.0001), low oestrogen and progesterone receptor content (P<0.01 and P=0.0001, respectively) and an unfavourable long-term survival (P<0.05). With Phaseolus vulgaris erythroagglutinin (e-PHA) and leucoagglutinin (l-PHA) a linear, rather inconsistent, staining at the level of the basement membranes was observed in the glands: this, also noted with LCA, appeared intact in normal and hyperplastic glands without cytological atypia, and fragmented or absent in malignant glandular structures and in most hyperplastic glands showing cytological atypia. It is concluded that changes in the distribution of lectin-binding molecules in the endometrial cells are associated with the malignant state, whilst the extent of Con-A-lat reflects the biological behaviour of the tumours.

Topics: Carcinoma, Endometrioid; Concanavalin A; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Immunoenzyme Techniques; Lectins; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Survival Rate

In a previous study we showed that endometrial carcinoma (EC) patients have a T cell deficiency manifested in a reduced ability to be stimulated in vitro by PHA and to produce IL-2. In an attempt to understand the mechanism responsible for this alteration we present in this paper a study on T cells characterized by the ability to form rosettes, with human erythrocytes, following Con-A activation (designated auto-rosette forming cells--ARFC). These cells are also known to manifest suppressive activity. We show that the frequency of ARFC in con-A activated peripheral blood leukocytes (PBMC) of EC patients is significantly (2-5 fold) higher than that of healthy age-matched controls or that of patients with stage--I colon or vaginal cancer. Endometrial carcinoma is known to be associated with long term exposure to estrogens unopposed by progestins. Examining the possible role of estrogens in increasing the frequency of ARFC from EC patients, we found that in vitro addition of estradiol to Con-A stimulated PBMC from healthy donors increased the frequency of ARFC to levels found in EC patients. Tamoxifen, an anti estrogen drug, reduced the frequency of the estrogen stimulated ARFC to the original low level. Our results suggest a dual role for estrogen in carcinogenesis as well as in immunomodulation.

Topics: Concanavalin A; Endometrial Hyperplasia; Estradiol; Estrogens; Female; Humans; In Vitro Techniques; Lymphocyte Activation; Middle Aged; Rosette Formation; T-Lymphocytes; Tamoxifen; Uterine Neoplasms