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Estrogen receptor α and β expression in a case matched series of serous and endometrioid adenocarcinomas of the ovary
1Indiana Women’s Oncology, St. Vincent Hospitals Indianapolis, TN University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Division of Gynecologic Oncology, Iowa City, IA, USA
*Corresponding Author(s): J.P. Geisler E-mail: jgeisler@indianawomensoncology.com
Objective: The purpose of this study was to analyze estrogen receptor alpha and beta (ER alpha, ER beta) expression in a stage and grade matched cohort of patients with serous and endometrioid adenocarcinoma of the ovary. Methods: Forty-two patients from 1991 to the present were found to have the diagnosis of endometrioid adenocarcinoma of the ovary and have tissue available for analysis. Of these 42, ten were selected for analysis. These were stage and grade matched with ten patients having serous adenocarcinoma of the ovary during the same time period. ER alpha and ER beta mRNA was detected by a multiplex RT-PCR and amplification of random hexamer generated cDNA using a housekeeping gene (G3PD) as a control for mRNA quality and quantity. Methylation specific PCR (MS-PCR) was used to correlate methylation of the ER alpha and ER beta CpG islands with mRNA expression status. Results: ER alpha expression was present in ten of ten endometrioid adenocarcinomas but in only five of ten serous carcinomas (chi(2), p = 0.01). ER beta expression was present in six of ten endometrioid adenocarcinomas and in four of ten serous caricinomas (chi(2), p = 0.65). Methylation of the ER alpha and ER beta CpG islands was found in tumors without mRNA expression but not in the tumors with mRNA expression (p = 0.005). Conclusions: ER alpha expression, but not ER beta expression, is significantly more common in endometrioid than serous adenocarcinomas of the ovary when controlled for stage and grade. The role of methylation in ER silencing may lead to potential therapeutic interventions.
Methylation; Estrogen receptor; Ovarian cancer; Serous; Endometrioid
J.P. Geisler,E. Buller,K.J. Manahan. Estrogen receptor α and β expression in a case matched series of serous and endometrioid adenocarcinomas of the ovary. European Journal of Gynaecological Oncology. 2008. 29(2);126-128.
[1] Jemal A., Murray T., Samuels A., Ghafoor A., Ward E., Thun M. J.: “Cancer Statistics 2003”. CA Cancer J. Clin., 2003, 53, 5.
[2] Zwart J., Geisler J.P., Geisler H.E.: “Five-year survival in patients with endometrioid carcinoma of the ovary versus those with serous carcinoma”. Eur. J. Gynaecol. Oncol., 1998, 19, 225.
[3] Tammela J., Geisler J.P., Eskew P.N., Jr., Geisler H.E.: “Clear cell carcinoma of the ovary: poor prognosis compared to serous carcinoma”. Eur. J. Gynaecol. Oncol., 1998, 19, 438.
[4] Hilton J.L., Geisler J.P., Rathe J.A., Hattermann-Zogg M.A., De Young B., Buller R.E.: “Inactivation of BRCA1 and BRCA2 in ovarian cancer”. J. Natl. Cancer Inst., 2002, 94, 1396.
[5] Shigemasa K., Tian X, Gu L., Shiroyama Y., Nagai N., Ohama K.: “Expression of cyclooxygenase-2 and its relationship to p53 accumulation in ovarian adenocarcinomas”. Int. J. Oncol., 2003, 22, 99.
[6] Geisler J.P., Geisler H.E., Miller G.A., Wiemann M.C., Zhou W., Crabtree W.: “p53 and bc1-2 in epithelial ovarian carcinoma: their value as prognostic indicators at a median of 60 months of followup”. Gynecol. Oncol., 2000, 77, 278.
[7] Geisler J.P., Geisler H.E., Miller G.A., Weimann M.C., Zhou W., Miller J., Crabtree W.: “Stratification of patients with epithelial ovarian carcinoma into high and low risk categories”. CME J. Gynecol. Oncol., 2000, 5, 231.
[8] Skilling J.S., Sood A.K., Niemann T., Lager D.J., Buller R.E.: “An abundance of p53 null mutations in ovarian cancer”. Oncogene, 1996, 13, 117.
[9] Rutherford T., Brown W.D., Sapi E., Aschkenazi S., Munoz A., Mor G.: “Absence of estrogen receptor-b expression in metastatic ovarian cancer”. Obstet. Gynecol., 2000, 96, 417.
[10] Esteller M., Silva J.M., Dominguez G., Bonilla F., Matias-Guiu X, Lerma E. et al.: “Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors”. J. Natl. Cancer Inst., 2000, 92, 564.
[11] Geisler J.P., Hatterman-Zogg M.A., Rathe J.A., Buller R.E.: “BRCA1 dysfunction is common in ovarian cancer”. J. Natl. Cancer Inst., 2002, 94, 61.
[12] Clark S.J., Harrison J., Paul C.L., Frommer M.: “High sensitivity mapping of methylated cytosines”. Nuc. Acid Res., 1994, 22, 2990.
[13] Herman J.G., Graff J., Myohanen S., Nelkin B.D., Baylin S.B.: “Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands”. Proc. Natl. Acad. Sci. USA, 1996, 93, 9821.
[14] Domann F.E., Rice J.C., Hendrix M.J.C., Futscher B.W.: “Epigenetic silencing of maspin gene expression in human breast cancers”. Int. J. Cancer, 2000, 85, 805.
[15] Sasaki M., Kotcherguina L., Dharia A., Fujimoto S., Dahiya R.: “Cytosine-phosphoguanine methylation of estrogen receptors in endometrial cancer”. Cancer Res., 2001, 61, 3262.
[16] Li L.C., Dahiya R.: “MethPrimer: designing primers for methylation PCRs”. Bioinformatics, 2002, 18, 1427.
[17] Shiozawa T., Itoh K., Horiuchi A., Konishi I., Fujii S., Nikaido T.: “Down-regulation of estrogen receptor by the methylation of the estrogen receptor gene in endometrial carcinoma”. Anticancer, 2002, 22, 139.
[18] Maeda K., Tsuda H., Hashiguchi Y., Yamamoto K., Inoue T., Ishiko O., Ogita S.: “Relationship between p53 pathway and estrogen receptor status in endometrioid-type endometrial cancer”. Hum. Pathol., 2002, 33, 386.
[19] O’Doherty A.M., Church S.W., Russell S.E., Nelson J., Hickey I.: “Methylation status of oestrogen receptor-alpha gene promoter sequences in human ovarian epithelial cell lines”. Br. J. Cancer, 2002, 86, 282.
[20] Geisler J.P., Hatterman-Zogg M.A., Rathe J.A., Buller R.E.: “BRCA1 dysfunction is common in ovarian cancer”. J. Natl. Cancer Inst., 2002, 94, 61.
[21] Geisler J.P., Sood A.K., Holmes R.J., Hatterman-Zogg M.A., Rathe J.A., Buller R.E.: “Mismatch repair gene expression defects contribute to microsatellite instability in ovarian cancer”. Cancer, 2003, 98, 2199.
[22] Geisler J.P., Buller R.E.: “Mismatch repair gene expression defects contribute to microsatellite instability in ovarian cancer”. Cancer, 2004, 1000, 2486.
[23] Li A.J., Baldwin R.L., Karlan B.Y.: “Estrogen and progesterone receptor subtype expression in normal and malignant epithelial ovarian cell cultures”. Am. J. Obstet. Gynecol., 2003, 189, 22.
[24] Geisler J.P., Geisler H.E., Wiemann M.C., Givens S.S., Zhou Z., Miller G.A.: “Quantification of p53 in epithelial ovarian cancer”. Gynecol. Oncol., 1997, 66, 435.
[25] Geisler J.P., Wiemann M.C., Miller G.A., Geisler H.E.: “Estrogen and progesterone receptor status as prognostic indicators in patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary”. Gynecol. Oncol., 1996, 60, 424.
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