Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium.
OBJECTIVE
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 > or =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 > or =2(+). Of 19 endometrial hyperplasias, 11 (58%) expressed any COX-2; with 6 (32%) having a score of > or =2(+). All 10 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.
Orejuela
Francisco J
FJ
Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas Health Science Center, Houston, TX 77025, USA.
Ramondetta
Lois M
LM
Smith
Judith
J
Brown
Jubilee
J
Lemos
Luciano B
LB
Li
Yang
Y
Hollier
Lisa M
LM
D000328:Adult; D051546:Cyclooxygenase 2; D004714:Endometrial Hyperplasia / Q000201:enzymology / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D012189:Retrospective Studies
D008565:Membrane Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases