OBJECTIVES: To develop a new immunohistochemical marker system for supplementation of the Noyes histological classification of the endometrium in women of child bearing age with regular menstrual cycles, and to employ this system to evaluate pathologic factors involved in endometriosis, and thus to ascertain if it is useful in diagnosis. MATERIALS AND METHODS: Endometrial biopsies were sampled from the posterior fundus of 41 (24 proliferative phases, 17 secretory phases) women with regular menstrual cycles (28-32 days), and each sample was immunhistochemically stained according to Noyes et al (1975) for determination of expression for extrogen receptor (ER), progesterone receter(PR), integrin alpha1, alpha4, beta3, COX-1 and COX-2. Then, the PR, the integrin beta3, and COX-2 which were clearly expressed in the luteal phase was with endometrial samples were obtained from 20 cases of normal patients (group 1) and 25 cases with endometriosis (group 2) after confirming the day of ovulation by sex steroid level measurements 7-8 days after ovulation. RESULTS: In the regular menstruation group the expression of ER showed a tendency to be increased in the proliferative phase and decreased in the secretory phase, and was the highest in the proliferative phase. However, PR in the stromal cells showed no change in the entire menstrual cycle while in the epithelial cells, PR reached a peak in the late proliferative phase and was almost absent in the secretory phase. Integrin alpha 1, alpha4, and beta3 expression in the epithelial cells was absent in the proliferative phase but alpha1 was expressed strongly in the early and mid secretory phases and disappeared in the late proliferative phase, while beta3, appeared after the mid secretory phase and continued to be expressed until the late secretory phase. Expression in the stromal cells was weak overall and did not show any cyclic pattern. COX-1 expression was shown as a cyclic pattern in the stromal and epithelial cells and was partcularly strongly expressed in the mid secretory phase of epithelial cells, and in the mid secretory and menstruation phase of stromal cells. In the endometrial epithelial cells there was strong expression during the entire cycle with stronger expression in the secretory phase compared to the prolferative phase. COX-2 was clearly expressed in the late proliferative, early and mid secretory phased in the stromal cells. No expression was observed in the proliferative phase of the epithelial cells, but which began to appear in the early secretory phase reaching a significant pattern from the mid secretory phase onwards. There was almost no expression in the stromal cells. In the cases with endometriosis showing normal endometrial maturation according to the Noyes classification, PR expression was increased while Integrin-beta3 expression was significantly decreased compared to the normal group. Also, COX-2 expression was slightly decreased in the stromal cells of patients with endometriosis while it was significantly increased in the stromal cells. CONCLUSION: Immunohistochemical markers can supplement the original Noyes classification of histological endometrial dating and therefore ascertain existing pathologic conditions. Particularly for patients with endometriosis with normally mature endometrial cells, changes in COX-2 and integrin expression patterns may assist in elucidating pathophysiologic mechanisms and therefore aid in the diagnosis of abnormal implantation conditions, and consequently determine a treatment modality.
Biopsy ; Child ; Classification ; Diagnosis ; Endometriosis* ; Endometrium* ; Epithelial Cells ; Female ; Humans* ; Integrin alpha1 ; Integrin beta3 ; Luteal Phase ; Menstrual Cycle ; Menstruation ; Ovulation ; Progesterone* ; Prostaglandin-Endoperoxide Synthases* ; Receptors, Progesterone* ; Stromal Cells