Please wait a minute...
European Journal of Gynaecological Oncology  2020, Vol. 41 Issue (3): 375-379    DOI: 10.31083/j.ejgo.2020.03.5054
Original Research Previous articles | Next articles
Decreased expression of estrogen receptors alpha and beta in peripheral blood lymphocytes from the endometrial cancer patients and women with endometriosis
Marcin Jedryka1(), Agnieszka Chrobak2, Anna Chelmonska-Soyta2, Daria Fijalkowska3, Rafal Matkowski1
1Department of Oncology, Wroclaw Medical University and Lower Silesian Oncology Center, Pl. Hirszfelda 12, 53-314 Wroclaw, Poland
2Polish Academy of Science, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland
3University of Wrocław, Faculty of Biotechnology, Joliot-Curie 14a, 50-383 Wrocław, Poland
Download:  PDF(196KB)  ( 319 ) Full text   ( 7 )
Export:  BibTeX | EndNote (RIS)      

Aim: Endometriosis and endometrial cancer are described as typical estrogen-dependent gynaecological diseases. The question arises if estrogens, working through their receptors, could influence the immunological activity of lymphocytes in these disorders. Here, we evaluated transcriptional expression of the estrogen receptors alpha and beta (ERα and ERβ) in T lymphocytes isolated from the peripheral blood in endometrial cancer and endometriosis patients. Methods: Peripheral blood was collected from ten patients with endometrial cancer, nine with endometriosis, and ten disease-free controls. After isolation of the T lymphocytes, purity was confirmed by flow cytometry and the relative level of ERα and ERβ mRNA was determined using RT-qPCR analysis. Results: Both ERα and ERβ were significantly decreased in T lymphocytes isolated from patients with either endometrial cancer or endometriosis when compared to the healthy controls. We measured no difference in the mRNA levels of ERα between endometrial cancer patients and endometriosis group, but ERβ expression in endometrial cancer women was twice as high than in the endometriosis group. Conclusion: Decreased transcription of nuclear estrogen receptor isoforms characterizes T lymphocytes from women with endometrial cancer and endometriosis.

Key words:  Endometriosis      Pelvic Pain      Endometrium Cancer      Steroid Hormones      Hormone Receptors      Molecular Medicine      Growth Factors     
Submitted:  29 October 2018      Accepted:  08 January 2019      Published:  15 June 2020     
Fund: Wroclaw Medical University(SUB.280.19.050)
*Corresponding Author(s):  Marcin Jedryka     E-mail:

Cite this article: 

Marcin Jedryka, Agnieszka Chrobak, Anna Chelmonska-Soyta, Daria Fijalkowska, Rafal Matkowski. Decreased expression of estrogen receptors alpha and beta in peripheral blood lymphocytes from the endometrial cancer patients and women with endometriosis. European Journal of Gynaecological Oncology, 2020, 41(3): 375-379.

URL:     OR

Table 1  - mRNA expression of ERα and ERβ from the isolated lymphocytes presented as mean ± standard deviation and median & interquartile range in three studied groups: healthy, endometriosis and endometrial cancer.
ER alpha ER beta
healthy endometriosis cancer healthy endometriosis cancer
Mean 4.67 1.80 1.96 16.78 1.84 4.12
Standard deviation ± 2.70 ± 1.41 ± 0.53 ± 11.92 ± 2.28 ± 4.37
Median 4.16 1.27 1.95 10.67 1.30 2.93
Interquartile range 2.83 0.80 0.17 15.80 1.49 1.38
Figure 1.  - The expression of estradiol receptors alpha and beta in the peripheral blood T lymphocytes from women with endometrial cancer, endometriosis and healthy control.

[1] Lambert K.C., Curran E.M., Judy B.M., Milligan G.N., Lubahn D.B., Estes D.M.: “Estrogen receptor alpha (ERalpha) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17beta-estradiol acts through ERalpha to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation”. J. Immunol., 2005, 175, 5716.
pmid: 16237062
[2] Phiel K.L., Henderson R.A., Adelman S.J., Elloso M.M.: “Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations”. Immunol. Lett., 2005, 97, 107.
doi: 10.1016/j.imlet.2004.10.007
[3] Pierdominici M., Maselli A., Colasanti T., Ortona E.: “Estrogen receptors profiles in human peripheral blond lymphocytes”. Immunol. Lett., 2010, 132, 79.
doi: 10.1016/j.imlet.2010.06.003 pmid: 20542061
[4] Shim G.J., Gherman D., Kim H.J., Omoto Y., Iwase H., Bouton D., et al.: “Differential expression of oestrogen receptors in human secondary lymphoid tissues”. J. Pathol., 2005, 208, 408.
pmid: 16294372
[5] Tai P., Wang J., Jin H., Song X., Song X., Yan J., et al.: “Induction of regulatory T cells by physiological levels of estrogen”. J. Cell. Physiol. 2008, 214, 456.
doi: 10.1002/jcp.21221 pmid: 17654501
[6] Rider V., Li X., Peterson G., Dawson J., Kimler B.F., Abdou N.I.: “Differential expression of estrogen receptors in women with systemic lupus erythematosus”. J. Rheumatol., 2006, 33, 1093.
[7] Maselli A., Conti F., Alessandri C., Colasanti T., Barbati C., Vomero M., et al.: “Low expression of estrogen receptor beta in T lymphocytes and high serum levels of anti-estrogen receptor alpha antibodies impact disease activity in female patients with systemic lupus erythematosus”. Biol. Sex. Differ., 2016, 7, 3.
pmid: 26759713
[8] Lax S.F., Pizer E.S., Ronnett B.M., Kurman R.J.: “Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation”. Human. Pathol., 1998, 29, 924.
[9] Ghering P.A., Linda Van Le ., Olatidoye B., Geradts J.: “Estrogen receptor status, determined by immunohistochemistry, as a predictor of the recurrence of stage I endometrial carcinoma”. Cancer, 1999, 8986, 2083.
[10] Sliwinski T., Sitarek P., Stetkiewicz T., Sobczuk A., Blasiak J.: “Polymorphism of the ERα and CYP1B1 genes in a Polish subpopulation”. J. Obstet. Gynaecol. Res., 2010, 36, 311.
doi: 10.1111/j.1447-0756.2009.01143.x pmid: 20492382
[11] Attar E., Bulun S.: “Aromatase inhibitors: the next generation of therapeutics for endometriosis”? Fertil. Steril., 2006, 85, 1307.
doi: 10.1016/j.fertnstert.2005.09.064 pmid: 16647373
[12] Halis G., Mechsner S., Ebert A.: “The diagnosis and treatment of deep infiltrating endometriosis”. Dtsch. Arztebl. Int. 2010, 107, 446.
[13] Stygar D., Westlund P., Eriksson H., Sahlin L.: “Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytes”. Clin. Endocrinol., 2006, 64, 74.
[14] Ning C., Xie B., Zhang L., Shan W., Yang B., Luo X., et al.: “Infiltrating macrophages induce ERalpha expression through an IL-17A-mediated epigenetic mechanizm to sensitize endometria cancer cells to estrogen”. Cancer Res., 2016, 76, 1354.
doi: 10.1158/0008-5472.CAN-15-1260 pmid: 26744532
[15] Berstein L.M., Tchernobrovkina A.E., Gamajunova V.B., Kovalevskij A.J., Vasilyev D.A., Chepik O.F., et al.: “Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer”. J. Cancer Res. Clin. Oncol., 2003, 129, 245.
doi: 10.1007/s00432-003-0427-9 pmid: 12695909
[16] Bulun S.E.: “ Endometriosis”. N. Engl. J. Med. 2009, 360, 268.
[17] Wallace A.E., Gibson D.A., Saunders P.T.K., Jabbour H.N.: “Inflammatory events in endometrial adenocarcinoma”.[J]. Endocrinol., 2010, 206, 141.
[18] Couse J.F., Korach K.S.: “Estrogen receptor null mice: what have we learned and where will they lead us”? Endocr. Rev., 1999, 20, 358.
[19] Hall J.M., McDonell D.P.: “The estrogen receptor β-isoform (ER β) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens”. Endocrinol. 1999, 140, 5566.
[20] Jazaeri A.A., Nunes K.J., Dalton M.S., Xu M., Shupnik M.A., Rice L.W.: “Well-differentiated adenocarcinomas and poorly-differentiated mixed mullerian tumors have altered ER and PR isoforms expressions”. Oncog., 2001, 20, 6965.
[21] Hale G.E., Hughes C.L., Cline J.M.: “Endometrial cancer: hormonal factors, the perimenopausal “window of risk”, and isoflavones”.[J]. Clin. Endocrinol. Metab., 2002, 87, 3.
[22] Xue Q., Lin Z., Cheng Y.H., Huang C.C., Marsh E., Yin P., et al.: “Promoter methylation regulates estrogen estrogen receptor 2 in human endometrium and endometriosis”. Biol. Reprod., 2007, 77, 681.
pmid: 17625110
[23] Jones R.K., Bulmer J.N., Searle R.F.: “Phenotypic and functional studies of leukocytes in human endometrium and endometriosis”. Hum. Reprod. Update, 1998, 4, 702.
[24] Harris H.A.: “Estrogen receptor-beta: recent lessons from in vivo studies”. Mol. Endocrinol., 2007, 21, 1.
pmid: 16556737
[1] R. Tinelli, S. Uccella, E. Cicinelli, R. Alfonso, F. Romano, L Nappi, G. Trojano. Primary papillary serous carcinoma presenting as acute ovarian torsion in postmenopausal woman: a case report[J]. European Journal of Gynaecological Oncology, 2020, 41(1): 155-156.
[2] A. Markowska, W. Bednarek, R. Jach, A. Czekała, J. Markowska. Uterine fibroids: a new insight into an old problem[J]. European Journal of Gynaecological Oncology, 2019, 40(6): 915-918.
[3] S. Kim, K. J. Min, S. Lee, J. H. Hong, J. K. Lee, N. W. Lee, J. Y. Song. Clear cell carcinoma arising from abdominal wall endometriosis with lymph node metastasis – a rare case report and review of the literature[J]. European Journal of Gynaecological Oncology, 2019, 40(6): 1047-1050.
[4] J.-Y. Zhou, Y. Zou, L.-Q. Wang, S.-F. Fang, Y. Luo, Q.-H. Xie, F. Wang, O.-P. Huang. Novel CARD14 mutations in Chinese samples with ovarian endometriosis[J]. European Journal of Gynaecological Oncology, 2019, 40(5): 765-769.
[5] S. Kabukcuoglu, B. Hayit. Histopathologic features of advanced stage endometrial carcinoma[J]. European Journal of Gynaecological Oncology, 2019, 40(4): 614-618.
[6] M. Terzic, I. Likic Ladjevic, N. Ladjevic, S. Terzic, J. Dotlic, M. Cekerevac, N. Arsenovic, A.S. Laganà, A. Vereczkey. Anaplastic T-cell lymphoma of the urinary bladder with unspecific clinical and radiological characteristics – a unique case report[J]. European Journal of Gynaecological Oncology, 2019, 40(1): 136-139.
[7] M. Terzic, S. Terzic, J. Dotlic, M. Dokic, M. Mitrovic, G. Bapayeva, N. Arsenovic, A.S. Lagana, M. Norton. Ovarian clear cell carcinoma associated with endometriosis: a case report and literature review[J]. European Journal of Gynaecological Oncology, 2019, 40(1): 166-169.
[8] M. M. Żyła, M. Nowak, T. Stetkiewicz, M. Kostrzewa, K. Księżakowska-Łakoma, M. Wilczyński, J. Danielska, J. R. Wilczyński. Malignant transformation of caesarean scar endometriosis – presentation of three case reports and review of the literature[J]. European Journal of Gynaecological Oncology, 2018, 39(5): 830-835.
[9] B.D. de-la-Noval, M.D. Diestro Tejeda, L. Yébenes, I. Zapardiel, A. Hernández Gutiérrez, J. De-Santiago García. Recurrent endometriosis following tibolone hormone replacement therapy after mucinous ovarian carcinoma[J]. European Journal of Gynaecological Oncology, 2018, 39(2): 310-313.
[10] R. Delic. Ovarian endometrioid carcinoma associated with diffuse pulmonary endometriosis: a case report[J]. European Journal of Gynaecological Oncology, 2018, 39(1): 143-145.
[11] S. Kabukcuoglu. Calretinin expression in endometriosis. Is calretinin positive tubal epithelium origin of fallopian tube carcinoma?[J]. European Journal of Gynaecological Oncology, 2017, 38(6): 905-909.
[12] L. Di Benedetto, A. Guarino, M. Mallozzi, D. Caserta. Association of endometrioid ovarian carcinoma arising from endometriosis, endometrioid endometrial carcinoma, and high-grade undifferentiated endometrial sarcoma: a case report[J]. European Journal of Gynaecological Oncology, 2017, 38(4): 638-641.
[13] A. Zwierzchowska, G. Panek, M. Gajewska, E. Barcz. Endometriotic lesions mimicking advanced ovarian cancer - A case report and a review of the literature[J]. European Journal of Gynaecological Oncology, 2017, 38(2): 303-307.
[14] S. Szegedi, M. Koppán, T. Varga, K. Kovács, H.R. Tinneberg, J. Bódis. Endometrioid adenocarcinoma arising from adenomyosis: a case report[J]. European Journal of Gynaecological Oncology, 2016, 37(6): 858-860.
[15] İ. Ulu, A. Çelik, B. Haliloğlu, E. İlter, A. Midi. Comparison of the histopathological results of the endometrial thickness detected by transvaginal ultrasound of symptomatic and asymptomatic postmenopausal women[J]. European Journal of Gynaecological Oncology, 2016, 37(4): 474-477.
No Suggested Reading articles found!