Ukr.Biochem.J. 2026; Volume 98, Issue 3, May-Jun, pp. 112-121

doi: https://doi.org/10.15407/ubj98.03.112

Association of estrogen and progesterone receptor status and metabolic hormones with tumor progression in endometrial cancer

09.06.2026   Uncategorized

I. H. Ali1, S. M. Hasan2*, N. H. Khedhir3, O. Mohsein4

1Middle Technical University, Community Health Technologies Department, Iraq;
2Department of Anesthesia Techniques, College of Health
and Medical Technologies, University of Mashreq, Baghdad, Iraq;
3Department of Pharmacy, Medical Technical Institute of Kirkuk,
Northern Technical University, Community Health Technologies Department, Iraq;
4Department of Medical Laboratory Techniques, Mazaya University College,
Main Laboratory Unit, Thi-Qar Health Directorate, Al Habbobi Teaching Hospital, Thi-Qar, Iraq;
*e-mail: saif.hasan@uom.edu.iq

Received: 27 February 2026; Revised: 27 April 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026

Background. It is recognized that endometrial physiology and carcinogenesis depend on the balan­ce of estrogen and progesterone. Eхpression status of estrogen (ER) and progesterone (PR) receptors has been utilized clinically as a prognostic predictor of endometrial cancer (EC). Nevertheless there is growing evidence that insulin resistance and changes in adipokine secretory system are also important risk factor of EC. Objective. To investigate the association between tumor estrogen and progesterone receptors expression combined with metabolic hormone serum levels and tumor progression in patients with endometrial cancer. Methods. The study included 100 patients with endometrial cancer patients and 50 age-matched healthy controls. Serum estradiol, progesterone, insulin, leptin and adiponectin were analyzed with a chemiluminescent immunoassay. Tumor tissue samples were stained using monoclonal antibodies against ER and PR with a standard streptavidin-biotin method. Nuclear staining ≥10% was considered positive. Results. It was shown that the majority of the tumors were ER-positive (68%) and PR-positive (54%) while 27% were double-nega­tive. Serum estradiol, leptin, and insulin levels were significantly higher in advanced-stage patients, while progesterone and adiponectin levels were significantly lower compared to early-stage patients. Correlation and regression results showed that the independent variables that predicted tumor progression were ER and PR negativity, high estradiol, high leptin, and low adiponectin. Conclusions. The loss of ER/PR expression and a metabolic hormonal imbalance – characterized by elevated levels of estradiol and leptin and reduced levels of adiponectin – are closely associated with the progression of endometrial cancer. These changes may contribute to proliferative signaling pathways and inflammatory processes, leading to increased tumor aggressiveness and disease progression.

Keywords: , , , , , ,

References:

  1. Gu B, Shang X, Yan M, Li X, Wang W, Wang Q, Zhang C. Variations in incidence and mortality rates of endometrial cancer at the global, regional, and national levels, 1990-2019. Gynecol Oncol. 2021;161(2):573-580. PubMed, CrossRef
  2. Lortet-Tieulent J, Ferlay J, Bray F, Jemal A. International Patterns and Trends in Endometrial Cancer Incidence, 1978-2013. J Natl Cancer Inst. 2018;110(4):354-361. PubMed, CrossRef
  3. Diep CH, Ahrendt H, Lange CA. Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes. Steroids. 2016;114:48-58. PubMed, PubMedCentral, CrossRef
  4. Chen H, Malentacchi F, Fambrini M, Harrath AH, Huang H, Petraglia F. Epigenetics of Estrogen and Progesterone Receptors in Endometriosis. Reprod Sci. 2020;27(11):1967-197 PubMed, CrossRef
  5. Przewoźny S, Rogaliński J, de Mezer M, Markowska A, Markowska J, Żurawski J. Estrogen Receptor (ER) and Progesterone Receptor (PgR) Expression in Endometrial Cancer-An Immunohistochemical Assessment. Diagnostics (Basel). 2024;14(3):322. PubMed, PubMedCentral, CrossRef
  6. Bhardwaj P, Brown KA. Obese Adipose Tissue as a Driver of Breast Cancer Growth and Development: Update and Emerging Evidence. Front Oncol. 2021;11:638918. PubMed, PubMedCentral, CrossRef
  7. Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Investig. 2016;26(1):25-42. PubMed, CrossRef
  8. Michalczyk K, Niklas N, Rychlicka M, Cymbaluk-Płoska A. The Influence of Biologically Active Substances Secreted by the Adipose Tissue on Endometrial Cancer. Diagnostics (Basel). 2021;11(3):494. PubMed, PubMedCentral, CrossRef
  9. Sidorkiewicz I, Jóźwik M, Niemira M, Krętowski A. Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA. Cancers (Basel). 2020;12(9):2559. PubMed, PubMedCentral, CrossRef
  10. Ghazi MH, Hassan EF, Ibrahim NH, Mohsein OA. Early Detection of Prostate Cancer Using Novel ELISA-Based Biomarkers: Insights into Inflammatory and Tumor-Specific Pathways. Asian Pac J Cancer Prev. 2025;26(10):3833-3839. PubMed, PubMedCentral, CrossRef
  11. Wang X, Xue Y. Clinicopathological characteristics and prognostic analysis of breast cancer with a hormone receptor status of ER(-)/PR(+). Front Endocrinol (Lausanne). 2023;14:1193592. PubMed, PubMedCentral, CrossRef
  12. Sgroi DC, Treuner K, Zhang Y, Piper T, Salunga R, Ahmed I, Doos L, Thornber S, Taylor KJ, Brachtel E, Pirrie S, Schnabel CA, Rea D, Bartlett JMS. Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study. Breast Cancer Res. 2022;24(1):90. PubMed, PubMedCentral, CrossRef
  13. BharathwajChetty B, Sajeev A, Vishwa R, Aswani BS, Alqahtani MS, Abbas M, Kunnumakkara AB. Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics. Cancer Metastasis Rev. 2024;43(1):321-362. PubMed, CrossRef
  14. Lappano R, Todd LA, Stanic M, Cai Q, Maggiolini M, Marincola F, Pietrobon V. Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment. Cancers (Basel). 2022;14(3):539. PubMed, PubMedCentral, CrossRef
  15. Byun D, Hong S, Ryu S, Nam Y, Jang H, Cho Y, Keum N, Oh H. Early-life body mass index and risks of breast, endometrial, and ovarian cancers: a dose-response meta-analysis of prospective studies. Br J Cancer. 2022;126(4):664-672. PubMed, PubMedCentral, CrossRef
  16. Secord AA, Hasselblad V, Von Gruenigen VE, Gehrig PA, Modesitt SC, Bae-Jump V, Havrilesky LJ. Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol. 2016;140(1):184-190. PubMed, PubMedCentral, CrossRef
  17. Muhammed TM, Farag AH, Hassan ZL, Mohsein OA. (). Comparative analysis of PSMA, PSA3, and TMPRSS2-ERG as diagnostic and prognostic biomarkers in prostate cancer patients. Int J Endocrinol (Ukraine). 2025;21(7):728-734. CrossRef
  18. Ofodire E. Hyperinsulinism gateway between diabetes and cancer: new roles for bifunctional antidiabetic – anticancer active somatostatins, IGF-1 inhibitors and insulin sensitizers. Adv Bioeng Biomed Sci Res. 2023;6(3):17-24. CrossRef
  19. Ramasubbu K, Devi Rajeswari V. Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review. Mol Cell Biochem. 2023;478(6):1307-1324. PubMed, CrossRef
  20. Hu X, Chen W, Li F, Ren P, Wu H, Zhang C, Gu K. Expression changes of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer and its clinical significance. Front Oncol. 2023;13:1053125. PubMed, PubMedCentral, CrossRef
  21. Smith D, Stewart CJR, Clarke EM, Lose F, Davies C, Armes J, Obermair A, Brennan D, Webb PM, Nagle CM, Spurdle AB. ER and PR expression and survival after endometrial cancer. Gynecol Oncol. 2018;148(2):258-266. PubMed, CrossRef
  22. Gamrani S, Boukansa S, Benbrahim Z, Mellas N, Fdili Alaoui F, Melhouf MA, Bouchikhi C, Banani A, Boubbou M, Bouhafa T, El Fatemi H. The Prognosis and Predictive Value of Estrogen Negative/Progesterone Positive (ER-/PR+) Phenotype: Experience of 1159 Primary Breast Cancer from a Single Institute. Breast J. 2022;2022:9238804. PubMed, PubMedCentral, CrossRef
  23. Senel F. The hormone receptor status in breast cancer and the relationship of subtypes with clinicopathological features. Indian J Pathol Microbiol. 2021;64(4):671-676. PubMed, CrossRef
  24. Millward DJ. Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr Res Rev. 2017;30(1):50-72. PubMed, CrossRef
  25. Ajeed AM, Abdullah NN, Al-Rikabi KG, Mohsein OA. Association of HPV viral load, estrogen receptor α signaling, and inflammatory serum biomarkers with cervical cancer progression. Regul Mech Biosyst. 2026;17(2):e26034. CrossRef
  26. Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet. 2016;293(2):247-269. PubMed, CrossRef
  27. Yang X, Wang J. The Role of Metabolic Syndrome in Endometrial Cancer: A Review. Front Oncol. 2019;9:744. PubMed, PubMedCentral, CrossRef
  28. Ding S, Madu CO, Lu Y. The Impact of Hormonal Imbalances Associated with Obesity on the Incidence of Endometrial Cancer in Postmenopausal Women. J Cancer. 2020;11(18):5456-5465. PubMed, PubMedCentral, CrossRef
  29. Yu K, Huang ZY, Xu XL, Li J, Fu XW, Deng SL. Estrogen Receptor Function: Impact on the Human Endometrium. Front Endocrinol (Lausanne). 2022;13:827724.
    PubMed, PubMedCentral, CrossRef
  30. Lv M, Chen P, Bai M, Huang Y, Li L, Feng Y, Liao H, Zheng W, Chen X, Zhang Z. Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma. Cancers (Basel). 2022;14(24):6210. PubMed, PubMedCentral, CrossRef
  31. Gallo M, Adinolfi V, Barucca V, Prinzi N, Renzelli V, Barrea L, Di Giacinto P, Ruggeri RM, Sesti F, Arvat E, Baldelli R; EOLO Group; Arvat E, Colao A, Isidori A, Lenzi A, Baldell R, Albertelli M, Attala D, Bianchi A, Di Sarno A, Feola T, Mazziotti G, Nervo A, Pozza C, Puliani G, Razzore P, Ramponi S, Ricciardi S, Rizza L, Rota F, Sbardella E, Zatelli MC. Expected and paradoxical effects of obesity on cancer treatment response. Rev Endocr Metab Disord. 2021;22(4):681-702. PubMed, CrossRef
  32. Storti G, Scioli MG, Kim BS, Terriaca S, Fiorelli E, Orlandi A, Cervelli V. Mesenchymal Stem Cells in Adipose Tissue and Extracellular Vesicles in Ovarian Cancer Patients: A Bridge toward Metastatic Diffusion or a New Therapeutic Opportunity? Cells. 2021;10(8):2117. PubMed, PubMedCentral, CrossRef
  33. Faisal NH, Obaid NAM, Ali NW, Al-Shawi AAA, Ibrahim RG, Hassan AN, Kadhum AJ, Mohsein OA, Luaibi IN. Green Synthesis of Silver Nanoparticles Using the Seeds of Lupinus luteus: Characterization and Assessment the Antibacterial and Anticancer Activities. Asian Pac J Cancer Prev. 2025;26(9):3405-3414. PubMed, PubMedCentral, CrossRef
  34. Huang Z, Huang L, Waters MJ, Chen C. Insulin and Growth Hormone Balance: Implications for Obesity. Trends Endocrinol Metab. 2020;31(9):642-654. PubMed, CrossRef
  35. Ahmed AW, Abdul-QaderKhuder H, Jasim SA, Mohsein OA. Hormonal profiles and metabolic changes in women diagnosed with concomitant Hashimoto’s thyroiditis and polycystic ovary syndrome via sonography. Eur J Clin Exp Med. 2025;23(3):596-604. CrossRef
  36. Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59. PubMed, PubMedCentral, CrossRef
  37. Yoder R, Kimler BF, Staley JM, Schwensen K, Wang YY, Finke K, O’Dea A, Nye L, Elia M, Crane G, McKittrick R, Pluenneke R, Madhusudhana S, Beck L, Shrestha A, Corum L, Marsico M, Stecklein SR, Godwin AK, Khan QJ, Sharma P. Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer. NPJ Breast Cancer. 2022;8(1):80. PubMed, PubMedCentral, CrossRef
  38. Hu T, Chen Y, Liu Y, Zhang D, Pan J, Long M. Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores. BMC Med Res Methodol. 2021;21(1):108. PubMed, PubMedCentral, CrossRef
  39. Wu N, Fu F, Chen L, Lin Y, Yang P, Wang C. Single hormone receptor-positive breast cancer patients experienced poor survival outcomes: a systematic review and meta-analysis. Clin Transl Oncol. 2020;22(4):474-485. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.