PARENT SESSION
PLATFORM SESSION 16. FEMALE REPRODUCTIVE TRACT II

Tuesday, August 3, 2004
4:30 PM–6:30 PM
Buchanan A202
Chair: William Okulicz Co-Chair: Julie Hastings

(559) GAIN OF OGP, AN ESTROGEN-REGULATED OVIDUCT-SPECIFIC GLYCOPROTEIN, IS ASSOCIATED WITH THE DEVELOPMENT OF ENDOMETRIAL HYPERPLASIA AND ENDOMETRIAL CANCER.

Woo, Michelle¹, Gilks, Blake², Alkushi, Abdulmohsen², Verhage, Harold³, Leung, Peter¹, Auersperg, Nelly¹, ¹ Department of Obstetrics and Gynecology, Vancouver, BC, Canada² Department of Pathology, Vancouver, BC, Canada³ Department of Obstetrics and Gynecology, Chicago, Illinois

ABSTRACT- The endometrium undergoes a wide range of phenotypic changes during carcinogenesis, reflecting the variable cellular differentiation in the Mullerian system. The most common endometrial cancers are low grade, estrogen-related endometrioid adenocarcinoms (EEC). Uterine papillary serous carcinomas (UPSC) are infrequent, but are clinically important due to their poor prognosis. We recently identified a marker of serous differentiation, oviduct-specific glycoprotein (OGP), in ovarian cancer. In this study, we investigated whether there was differential expression of OGP in archived human specimens of normal, hyperplastic and malignant endometrium via immunohistochemistry. OGP was absent in the functionalis layer of proliferative, secretory or menstrual endometria. However, there was focal OGP expression in the basalis layer, where the stem cells reside, in 8 of 15 cases. On average, atypical hyperplastic endometria (24/25 positive) stained more intensely than hyperplastic endometria (13/14 positive) (p=0.05), with varying percentages of positive cells. Using a score of 1-3, the mean staining indices (Intensity Score X % of Positive Cells Score) for hyperplasia and atypical hyperplasia were 4.7 and 5.5, respectively (p=0.1). OGP staining was lower in endometrial cancers, with staining indices of 2.8 for Grade 1 EECs (15 cases), 1.1 for Grade 3 EECs (9 cases), and 0.9 for UPSCs (8 cases). There were significant differences in staining between normal endometria and all hyerplasias (p<0.0001), and all hyperplasias with all carcinomas (p<0.0001). In an endometrial cancer tissue array, 176 cases with known prognoses were examined for OGP expression. Of 139 EECs, 11 cases were strongly OGP positive while the other 128 cases were negative. All 37 cases of non-endometrioid carcinomas were negative. Analysis of Kaplan-Meier curves with log rank statistics showed a trend towards significance, for strong OGP staining being a predictor of good prognosis (p=0.1). Our results indicate that OGP, normally secreted by the oviduct, reappears in the stem cells of endometrial glands reflecting their common embryonic origin. Furthermore, upregulation of OGP appears with development of hyperplasia and preneoplastic lesions, with levels falling with progression to carcinoma. Supported by NCIC.

KEY WORDS: hyerplasia, prognosis, endometrial carcinoma, oviductal glycoprotein