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Differential Expression of Estrogen Receptor- and -ß Messenger RNAs as a Potential Marker of Ovarian Carcinogenesis¹

Services de Biologie Cellulaire [P. P., J-M. R., H. R., T. M.] et de Gynécologie-Obstétrique [F. L.], Centre Hospitalier Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier; Unité INSERM 148 [P. P., J-M. R., P. R., H. R., T. M.] et Unité INSERM 439 [P. N.], 34095 Montpellier; and Service de Biologie Cellulaire, Faculté de Médecine de la Timone, 13385 Marseille [M. G.], France

Although estrogen receptor (ER)- is expressed in both benign and malignant ovarian tumors, the role of ER in ovarian carcinogenesis of epithelial tumors is still unknown. In view of the recent characterization of ER-ß, a second form of ER that seems to be highly expressed in ovaries, we reexamined this issue by studying the relative expression of ER- and -ß in human ovarian tumor progression.

We developed a competitive PCR assay based on coamplification of the two ERs in target nucleotide sequences displaying a high homology (exons 3 and 4). Coamplification experiments with varying amounts of plasmids containing ER- and -ß cDNAs showed that this assay was reliable for discriminating as little as a 2-fold difference in the initial ER-:ER-ß cDNA ratio. The relative expression of ER- compared with ER-ß mRNAs was studied in human ovarian cancer cell lines (n = 5) and in normal ovaries (n = 6), then in human benign and malignant tumor samples including ovarian cysts (n = 24), borderline tumors (n = 3), and cancers (n = 10). In normal ovaries, ER-ß mRNA was the predominant ER form, whereas in ovarian cancer cell lines ER- mRNA was markedly increased as compared with ER-ß. In benign and borderline tumors, ER-ß mRNA was detected in 78% of tumors, whereas ER- mRNA was detected in 29%. In ovarian carcinomas, both ER- and -ß mRNAs were expressed in 80% of tumors. The ER-:ER-ß mRNA ratio was >1 in only one cyst sample (4%). In contrast, the ER-:ER-ß mRNA ratio was markedly increased in ovarian cancers because 60% showed an ER-:ER-ß mRNA >1. In situ hybridization experiments showed overlapping tissular distribution of ER-ß and - expression in cancers and cysts, with a main localization in the epithelium and only a low level of expression in stromal cells.

In summary, we found an increase in the ER-:ER-ß mRNA ratio in ovarian carcinomas as compared with normal ovaries and cysts. These data suggest that overexpression of ER- relative to ER-ß mRNA may be a marker of ovarian carcinogenesis.

¹ Supported by the "Center Hospitalier Universitaire de Montpellier," the "Ligue Nationale de Recherche Contre le Cancer," and the "Institut National de la Santé et de la Recherche Médicale."

² To whom requests for reprints should be addressed, at Laboratoire de Biologie Cellulaire, Hôpital Arnaud de Villeneuve, 271, Av G. Giraud, 34295 Montpellier Cedex 5, France.

Received 7/13/98. Accepted 10/ 5/98.

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