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Expression of estrogen receptors a and in two uterine mesenchymal tumors after prolonged tamoxif en therapy. Report of two cases
11 st Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Hippokrateio General Hospital, Thessaloniki, Greece
2Department of Pathology, Hippokrateio General Hospital, Thessaloniki, Greece
*Corresponding Author(s): M. Zafrakas E-mail:
Introduction: Tamoxifen therapy is associated with an increased risk of endometrial carcinoma, and possibly uterine sarcomas. Little is known about hormone receptor expression in mesenchymal tumors of the uterus after tamoxifen therapy.
Cases: The cases of two patients with uterine mesenchymal tumors after prolonged tamoxifen therapy due to breast cancer are presented. The expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) and progesterone receptors (PR) was studied immunohistochemically in both cases. Both tumors were negative for ERalpha and positive for ERbeta. In the first case the tumor was negative for PR, while in the second only 20% of nuclei were PR-positive.
Conclusions: Consistent with previous studies, uterine mesenchymal tumors after tamoxifen therapy do not express ERalpha. The results of the present report provide for the first time evidence that tamoxifen might exert a stimulatory effect on the uterus, at least during tumor progression, through ERbeta but not through ERalpha.
Tamoxifen; Uterine sarcoma; Mesenchymal tumors; Estrogen receptors
M. Zafrakas,E. Kostopoulou,K. Dragoumis,T. Mikos,J. Papadimas,J. Bontis. Expression of estrogen receptors a and in two uterine mesenchymal tumors after prolonged tamoxif en therapy. Report of two cases. European Journal of Gynaecological Oncology. 2004. 25(4);530-533.
[1] Mourits M.J., De Vries E.G., Willemse P.H., Ten Hoor K.A., Hollema H., Van der Zee A.G.: "Tamoxifen treatment and gynecologic side effects: a review". Obstet. Gynecol., 2001, 97, 855.
[2] Wickerham D.L., Fisher B., Wolmark N., Bryant J., Costantino J., Bernstein L., Runowicz C.D.: "Association of tamoxifen and uterine sarcoma". J. Clin. Oncol., 2002, 20 (11), 2758.
[3] Fisher B., Dignam J., Wolmark N., Wickerham D.L., Fisher E.R., Mamounas E. et al.: "Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B- 24 randomised controlled trial". Lancet, 1999, 353 (9169), 1993.
[4] Fisher B., Costantino J.P., Wickerham D.L., Redmond C.K., Kavanah M., Cronin W.M. et al.: "Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study". J. Natl. Cancer Inst., 1998, 90 (18), 1371.
[5] Fisher B., Costantino J.P., Redmond C.K., Fisher E.R., Wickerham D.L., Cronin W.M.: "Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14". J. Natl. Cancer Inst., 1994, 86 (7), 527.
[6] Wysowski D.K., Honig S.F., Beitz J.: "Uterine sarcoma associated with tamoxifen use". N. Engl. J. Med., 2002, 346 (23), 1832.
[7] Gottlieb S.: "Tamoxifen may increase risk of uterine sarcoma". Br. Med. J, 2002, 325 (7354), 7.
[8] Twombly R.: "FDA issues warning about 'new' tamoxifen risk". J. Natl. Cancer Inst., 2002, 94 (15), 1122.
[9] Bergman L., Beelen M.L., Gallee M.P., Hollema H., Benraadt J., van Leeuwen F.E.: "Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen". Lancet, 2000, 356 (9233), 881.
[10] Liao J.B., Lin J.Y.: "Estrogen receptor expression in an endometrial stromal sarcoma after tamoxifen therapy". Eur. J. Gynaecol. Oncol., 2001, 22 (6), 417.
[11] Bell S., Kempson R., Hendrickson M.: "Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases". Am. J. Surg. Pathol., 1994, 18, 535.
[12] Neven P., Shepherd J.H., Lowe D.G.: "Tamoxifen and the gynaecologist". Br. J. Obstet. Gynaecol., 1993, 100, 893.
[13] Altaras M.M., Aviram R., Cohen I., Cordoba M., Yarkoni S., Beyth Y.: "Role of prolonged stimulation of tamoxifen therapy in the etiology of endometrial sarcomas". Gynecol. Oncol., 1993, 49 (2), 255.
[14] Clarke M.R.: "Uterine malignant mixed ·mullerian tumor tn a patient on long-term tamoxifen therapy for breast cancer". Gynecol. Oncol., 1993, 51 (3), 411.
[15] Beer T.W., Buchanan R., Buckley C.H.: "Uterine stromal sarcoma following tamoxifen treatment". J. Clin. Pathol., 1995, 48 (6), 596.
[16] Clement P.B., Oliva E., Young R.H.: "Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: A report of six cases and a review of tamoxifen associated endometrial lesions". Int. J. Gynaecol. Pathol., 1996, 15, 222.
[17] McCluggage W.G., McManus D.T., Lioe T.F., Hill C.M.: "Uterine carcinosarcoma in association with tamoxifen therapy". Br. J. Obstet. Gynaecol., 1997, 104, 748.
[18] Mourits M.J.E., Hollema H., Willemse P.H.B., De Vries E.G.E., Aalders J.G., Van der Zee A.G.J.: "Adenosarcoma of the uterus following tamoxifen for breast cancer". Int. J. Gynecol. Cancer, 1998, 8, 168.
[19] Pang L.C.: "Endometrial stromal sarcoma with sex cord-like differentiation associated with tamoxifen therapy". South Med. J., 1998, 91 (6), 592.
[20] Fotiou S., Hatjieleftheriou G., Kyrousis G., Kokka F., Apostolikas N.: "Long-term tamoxifen treatment: A possible aetiological factor in the development of uterine carcinosarcoma: Two case-reports and review of the literature". Anticancer Res., 2000, 20, 2015.
[21] White I.: "Anti-oestrogenic drugs and endometrial cancers". Toxicol. Letters, 2001, 120, 21.
[22] Enmark E., Pelto-Huikko M., Grandien K.. Lagercrantz S., Fried G., Nordenskjold M., Gustafsson J.: "Human estrogen receptor beta-Gene structure, chromosomal localization, and expression pattern". J. Clin. Endocrinol. Metab., 1997, 82, 4258.
[23] Watanabe T., Inoue S., Ogawa S., Ishii Y., Hiroi H., Ikeda K. et al.: "Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta". Biochem. Biophys Res. Comm., 1997, 236 (1), 140.
[24] Tremblay G., Tremblay A.. Copeland N., Gilbert D., Jenkins N., Labrie F., Giguere V.: "Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta". Mol Endocrinol., 1997, 11, 353.
[25] Cohen I., Beyth Y., Altaras M., Shapira J., Tepper R., Cardoba M et al. "Estrogen and progesterone receptor expression in postmenopausal tamoxifen-exposed endometrial pathologies" Gynecol. Oneal., 1997, 67, 8.
[26] Schwartz L., Krey L., Demopoulos R., Goldstein S., Nachtigall L., Mittal K.: "Alterations in steroid hormone receptors in the tamoxif en-treated endometrium". Am. J. Obstet. Gynecol., 1997, 176, 129.
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