Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium

Objectives. To determine whether cyclooxygenase-2 (COX-2) expression is seen in endometrial cancer, endometrial hyperplasia, and normal endometria and whether it correlates with expression of estrogen and progesterone receptors. Methods. The study was a retrospective, IRB-approved analysis of biopsy samples from 14 patients with endometrial adenocarcinoma, 19 with endometrial hyperplasias, and 10 with normal endometrium. Excluded were samples from women with a history of pelvic radiation, NSAID use, or treatment with hormones during previous year. Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissues. Expression of COX-2, estrogen and progesterone receptors were scored according to the proportion of positive-staining cells: 1(+), < 10%; 2(+), 10-50%; and 3(+), > 50%. A score >= 2(+) was considered positive. Fisher's exact test and analysis of variance were used to compare proportions and continuous variables, respectively. Results. Overexpression of COX-2 was seen in 4 (29%) of the endometrial cancers, 6 (32%) of the endometrial hyperplasia, and 4 (20%) of the normal endometria. These differences were not statistically significant (P = 0.90). No COX-2 expression was found in stromal tissue. Of 14 endometrial cancers, 7 (50%) expressed any COX-2, with 4 (29%) having an expression score of >= 2(+). Of 19 endometrial hyperplasias, 11 (58%) expressed any COX-2; with 6 (32%) having a score of >= 2(+). All 110 normal endometria showed only 1(+) expression. No significant differences were detected in COX-2 expression by grade or stage of cancer. Although 100% and 95% of both hyperplasia and normal endometrium samples expressed in estrogen and progesterone receptors, respectively, only 71% and 79% of endometrial cancers expressed estrogen and progesterone receptors ( P = 0.01). A nonparametric trend was performed to detect a relationship, between COX-2 and estrogen receptor or progesterone receptor expression; no significant trend was found. Conclusions. In this study, the immunohistochemical analysis showed a trend toward increased COX-2 expression in endometrial cancer and hyperplasia compared to normal endometria. A larger sample size is needed to confirm these results. The increased COX-2 expression in hyperplasia may signify an early step in carcinogenesis. These findings may represent an important treatment opportunity for synergism in the hormonal therapy of endometrial cancer. (c) 2005 Published by Elsevier Inc.