CYTOKERATIN-8, CYTOKERATIN-18 AND CYTOKERATIN-19 IN ENDOMETRIAL EPITHELIAL-CELLS DURING THE NORMAL MENSTRUAL-CYCLE AND IN WOMEN RECEIVING NORPLANT

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament protein family. They are expressed in all simple epithelial tissues, including endometrium, and are recognised as dynamic structur es that can be affected by numerous external factors. The Norplant sys tem is a subdermal slow release levonorgestrel implant commonly used a s a long-acting progestogen contraceptive. Norplant implants have been shown to have atrophic effects on endometrial epithelial and stromal cells, and cause a range of endometrial bleeding problems among users. The aim of this study is to describe changes in the immunohistochemic al expression and distribution of cytokeratins 8, 18 and 19 in endomet rial epithelial cells of Norplant implants users and normal menstrual cycle controls. Endometrial biopsies were collected from 65 control no rmal cycle women and 37 Norplant implants acceptors. The normal menstr ual cycle was classified histologically into 9 stages; one menstrual, five proliferative and three secretory. Norplant implants bleeding pat terns were categorised into 6 groups according to current World Health Organisation (WHO) definitions; amenorrhoea, frequent bleeding, infre quent bleeding, irregular bleeding, ''normal'' bleeding, and prolonged bleeding. The tissues were fixed in formalin, embedded in paraffin, a nd stained imunohistochemically. Semiquantitative scoring of the stain ing intensity was performed. Apical versus basal intracellular cytoker atin distribution was also evaluated. The staining intensity was signi ficantly stronger in control endometrial tissue compared to Norplant i mplants tissue. In control tissues, cytokeratins were predominantly lo cated in the apical region of epithelial cells (52% of biopsies) and i n Norplant implants tissues they were predominantly distributed equall y between the apical and basal portions of epithelial cells (43% of bi opsies). There was no particular cytokeratin distribution pattern asso ciated with the different stages of normal cycle or the different Norp lant implants bleeding patterns. It was concluded that long-term expos ure to levonorgestrel significantly reduced the cytokeratin expression in endometrial epithelial cells (P < 0.001).