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Endometrial poliplerde CD56 gen ekspresyonu ve uNK hücre oranının moleküler ve immünohistokimyasal olarak değerlendirmesi

Year 2025, Volume: 50 Issue: 4, 964 - 971, 22.12.2025
https://doi.org/10.17826/cumj.1716574

Abstract

Amaç: Bu çalışmada endometriyal poliplerde uterin doğal öldürücü (uNK) hücre yoğunluğu ve CD56 (NCAM1) gen ekspresyon düzeyinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: 18-40 yaş arası kadınlardan alınan 50 endometriyal polip ve 50 normal endometriyum örneği immünohistokimyasal ve qPCR analizleri ile değerlendirilmiştir. CD56 pozitif uNK hücreleri immünboyama ile sayılmış ve gen ekspresyon düzeyleri 2-ΔΔCt yöntemi ile hesaplanmıştır.
Bulgular: Kontrol grubunda CD56 gen ekspresyon düzeyinin daha yüksek olduğu belirlenmiştir (ortalama Ct değeri: kontrol grubu ≈ 32; polip grubu ≈ 27). İmmünohistokimyasal analizde ise CD56+ hücre yüzdesi kontrol grubunda ortanca %15,2 (dağılım: %5,4–24,8) iken, polip grubunda ortanca %9,8 (dağılım: %2,1–19,7) bulunmuştur.
Sonuç: Endometriyal poliplerde CD56 gen ekspresyonu ve uNK hücre oranındaki azalma gözlenmiştir. Bu veriler lezyonların bağışıklık mikroçevresinde düzenleyici bir bozulma olabileceğini göstermektedir. Bulgular poliplerin doğurganlık ve endometriyal reseptivite üzerindeki etkilerini açıklamada önemlidir.

Ethical Statement

Tarih: 09.02.2024 Sayı: 2

Project Number

no project number

References

  • Triantafyllidou O, Korompokis I, Chasiakou S, Bakas P, Kalampokas T, Simopoulou M, et al. Impact of hysteroscopic polypectomy on IVF outcomes in women with unexplained infertility. J Clin Med. 2024;13:4755.
  • de Almeida ECSA, Nogueira AA, dos Reis FJC, Ramalho LNZ, Zucoloto S. Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women. Maturitas. 2004;49:229-33.
  • Zhang XX, Wu XH. Decreased CD56+ CD16‐CD94+ uNK cells in the mid‐luteal phase in women with recurrent implantation failure are associated with IL‐15 deficiency. Am J Reprod Immunol. 2023;90:e13794.
  • Chiu CSC, Yeh LY, Pan SH, Li SH. Transcriptomic analysis reveals intrinsic abnormalities in endometrial polyps. Int J Mol Sci. 2024;25:2557.
  • El-Hamarneh T, Hey-Cunningham AJ, Berbic M, Al-Jefout M, Fraser IS, Black K. Cellular immune environment in endometrial polyps. Fertil Steril. 2013;100:1364-72.
  • Rao VA, Kurian NK, Rao KA. Cytokines, NK cells and regulatory T cell functions in normal pregnancy and reproductive failures. Am J Reprod Immunol. 2023;89:e13667.
  • Reis JL, Rosa NN, Martins C, Ângelo-Dias M, Borrego LM, Lima J. The role of NK and T cells in endometriosis. Int J Mol Sci. 2024;25:10141.
  • Kanter JR, Mani S, Gordon SM, Mainigi M. Uterine natural killer cell biology and role in early pregnancy establishment and outcomes. F&S Rev. 2021;2:265-86.
  • Guan D, Chen Z, Zhang Y, Sun W, Li L, Huang X. Dual role of natural killer cells in early pregnancy: immunopathological implications and therapeutic potential in recurrent spontaneous abortion and recurrent implantation failure. Cell Prolif. 2025;58:e70037.
  • Sowparani S, Mahalakshmi P, Sweety JP, Francis AP, Dhanalekshmi UM, Selvasudha N. Ubiquitous neural cell adhesion molecule (NCAM): potential mechanism and valorisation in cancer pathophysiology, drug targeting and molecular transductions. Mol Neurobiol. 2022;59:5902-24.
  • Postnikova A, Tello J, Alvarez M, Lee G, Ali I, Field CM et al. Depletion of a neural cell adhesion molecule disrupts both epithelial and germ layer identity in sea anemone embryos. bioRxiv. 2025-08.
  • Kofod L, Lindhard A, Hviid TVF. Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women. Hum Immunol. 2018;79:693-701.
  • Kamoi M, Fukui A, Kwak-Kim J, Fuchinoue K, Funamizu A, Chiba H et al. NK22 cells in the uterine mid-secretory endometrium and peripheral blood of women with recurrent pregnancy loss and unexplained infertility. Am J Reprod Immunol. 2015;73:557-67.
  • Hong IS. Endometrial stem/progenitor cells: properties, origins, and functions. Genes Dis. 2023;10:931-47.
  • Lebedeva OP, Zhukova IO, Kozarenko ON, Pakhomov SP. CD16 and CD56 mRNA expression in decidua of patients with missed and spontaneous abortions. J Minim Invasive Gynecol. 2021;28:S91-2.
  • Guo L, Gu F, Tan J, Luo L, Gao J, Zhou C. Multiple endometrial polyps is associated with higher risk of chronic endometritis in reproductive-aged women. J Obstet Gynaecol Res. 2021;47:389-96.
  • Aksak T, Askin A, Polat S, Ürünsak İF, Karaoğlan Ö. Immunohistochemical examination of PNAd, α4β1 integrin and MUC-2 expressions in the secretary phase endometrium of women diagnosed with recurrent implantation failure. J Reprod Immunol. 2025;167:104420.
  • Von Woon E, Greer O, Shah N, Nikolaou D, Johnson M, Male V. Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2022;28:548-82.
  • Southcombe JH, Mounce G, McGee K, Elghajiji A, Brosens J, Quenby S et al. An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage. Sci Rep. 2017;7:41335.
  • Chen Z, Halford NG, Liu C. Real-time quantitative PCR: primer design, reference gene selection, calculations and statistics. Metabolites. 2023;13:806.
  • Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale (NJ): Lawrence Erlbaum Associates; 2013.
  • Zippl AL, Kyvelidou C, Frank M, Gapp E, Reiser E, Braun AS et al. The impact of GnRH agonists on endometrial immune cells in patients with adenomyosis: a prospective cohort study. BMC Med. 2025;23:338.
  • Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L et al. Immunological changes associated with adenomyosis: a systematic review. Hum Reprod Update. 2021;27:108-29.
  • Sfakianoudis K, Rapani A, Grigoriadis S, Pantou A, Maziotis E, Kokkini G et al. The role of uterine natural killer cells on recurrent miscarriage and recurrent implantation failure: from pathophysiology to treatment. Biomedicines. 2021;9:1425.
  • Chiu CSC, Yeh LY, Pan SH, Li SH. Transcriptomic analysis reveals intrinsic abnormalities in endometrial polyps. Int J Mol Sci. 2024;25:2557.
  • Dibi RP, Zettler CG, Vanin CMDM, Ribeiro RVP, Oliveira JMD, Kremer TG et al. Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study. Sao Paulo Med J. 2020;138:64-8.
  • Ryu KJ, Kim MS, Lee JY, Nam S, Jeong HG, Kim T et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022;5:e2243951.
  • Mangla M, Palo S, Kanikaram PK, Raja Shekar P, Setty A. Comparative immuno-profiling of proliferative and disordered proliferative endometrium in anovulatory abnormal uterine bleeding. J Obstet Gynaecol Res. 2025;51:e70032.
  • Shivhare SB, Bulmer JN, Innes BA, Hapangama DK, Lash GE. Menstrual cycle distribution of uterine natural killer cells is altered in heavy menstrual bleeding. J Reprod Immunol. 2015;112:88-94

Molecular and immunohistochemical evaluation of CD56 gene expression and uNK cell percentage in endometrial polyps

Year 2025, Volume: 50 Issue: 4, 964 - 971, 22.12.2025
https://doi.org/10.17826/cumj.1716574

Abstract

Purpose: This study aimed to investigate the the percentage of uterine natural killer (uNK) cells and the expression level of CD56 (NCAM1) in endometrial polyps.
Materials and Methods: Endometrial tissue samples were obtained from women aged 18–40 years, including 50 with polyps and 50 controls. Samples were analyzed by immunohistochemistry and quantitative PCR (qPCR). CD56-positive uNK cells were quantified by immunostaining, and gene expression was assessed using the 2-ΔΔCt method.
Results: CD56 expression was significantly higher in the control group than in the polyp group (mean Ct values: control ≈ 32; polyp ≈ 27). Immunohistochemical analysis showed that the median percentage of CD56+ cells was 15.2% (range 5.4–24.8%) in the control group and 9.8% (range 2.1–19.7%) in the polyp group.
Conclusion: Endometrial polyps were associated with a significant reduction in CD56 gene expression and uNK cell percentage. These findings indicate a disruption of the local immune microenvironment, which may help explain the negative impact of polyps on fertility and endometrial receptivity.

Ethical Statement

Date: 09.02.2024 Number: 2

Supporting Institution

no supporting

Project Number

no project number

References

  • Triantafyllidou O, Korompokis I, Chasiakou S, Bakas P, Kalampokas T, Simopoulou M, et al. Impact of hysteroscopic polypectomy on IVF outcomes in women with unexplained infertility. J Clin Med. 2024;13:4755.
  • de Almeida ECSA, Nogueira AA, dos Reis FJC, Ramalho LNZ, Zucoloto S. Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women. Maturitas. 2004;49:229-33.
  • Zhang XX, Wu XH. Decreased CD56+ CD16‐CD94+ uNK cells in the mid‐luteal phase in women with recurrent implantation failure are associated with IL‐15 deficiency. Am J Reprod Immunol. 2023;90:e13794.
  • Chiu CSC, Yeh LY, Pan SH, Li SH. Transcriptomic analysis reveals intrinsic abnormalities in endometrial polyps. Int J Mol Sci. 2024;25:2557.
  • El-Hamarneh T, Hey-Cunningham AJ, Berbic M, Al-Jefout M, Fraser IS, Black K. Cellular immune environment in endometrial polyps. Fertil Steril. 2013;100:1364-72.
  • Rao VA, Kurian NK, Rao KA. Cytokines, NK cells and regulatory T cell functions in normal pregnancy and reproductive failures. Am J Reprod Immunol. 2023;89:e13667.
  • Reis JL, Rosa NN, Martins C, Ângelo-Dias M, Borrego LM, Lima J. The role of NK and T cells in endometriosis. Int J Mol Sci. 2024;25:10141.
  • Kanter JR, Mani S, Gordon SM, Mainigi M. Uterine natural killer cell biology and role in early pregnancy establishment and outcomes. F&S Rev. 2021;2:265-86.
  • Guan D, Chen Z, Zhang Y, Sun W, Li L, Huang X. Dual role of natural killer cells in early pregnancy: immunopathological implications and therapeutic potential in recurrent spontaneous abortion and recurrent implantation failure. Cell Prolif. 2025;58:e70037.
  • Sowparani S, Mahalakshmi P, Sweety JP, Francis AP, Dhanalekshmi UM, Selvasudha N. Ubiquitous neural cell adhesion molecule (NCAM): potential mechanism and valorisation in cancer pathophysiology, drug targeting and molecular transductions. Mol Neurobiol. 2022;59:5902-24.
  • Postnikova A, Tello J, Alvarez M, Lee G, Ali I, Field CM et al. Depletion of a neural cell adhesion molecule disrupts both epithelial and germ layer identity in sea anemone embryos. bioRxiv. 2025-08.
  • Kofod L, Lindhard A, Hviid TVF. Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women. Hum Immunol. 2018;79:693-701.
  • Kamoi M, Fukui A, Kwak-Kim J, Fuchinoue K, Funamizu A, Chiba H et al. NK22 cells in the uterine mid-secretory endometrium and peripheral blood of women with recurrent pregnancy loss and unexplained infertility. Am J Reprod Immunol. 2015;73:557-67.
  • Hong IS. Endometrial stem/progenitor cells: properties, origins, and functions. Genes Dis. 2023;10:931-47.
  • Lebedeva OP, Zhukova IO, Kozarenko ON, Pakhomov SP. CD16 and CD56 mRNA expression in decidua of patients with missed and spontaneous abortions. J Minim Invasive Gynecol. 2021;28:S91-2.
  • Guo L, Gu F, Tan J, Luo L, Gao J, Zhou C. Multiple endometrial polyps is associated with higher risk of chronic endometritis in reproductive-aged women. J Obstet Gynaecol Res. 2021;47:389-96.
  • Aksak T, Askin A, Polat S, Ürünsak İF, Karaoğlan Ö. Immunohistochemical examination of PNAd, α4β1 integrin and MUC-2 expressions in the secretary phase endometrium of women diagnosed with recurrent implantation failure. J Reprod Immunol. 2025;167:104420.
  • Von Woon E, Greer O, Shah N, Nikolaou D, Johnson M, Male V. Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2022;28:548-82.
  • Southcombe JH, Mounce G, McGee K, Elghajiji A, Brosens J, Quenby S et al. An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage. Sci Rep. 2017;7:41335.
  • Chen Z, Halford NG, Liu C. Real-time quantitative PCR: primer design, reference gene selection, calculations and statistics. Metabolites. 2023;13:806.
  • Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale (NJ): Lawrence Erlbaum Associates; 2013.
  • Zippl AL, Kyvelidou C, Frank M, Gapp E, Reiser E, Braun AS et al. The impact of GnRH agonists on endometrial immune cells in patients with adenomyosis: a prospective cohort study. BMC Med. 2025;23:338.
  • Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L et al. Immunological changes associated with adenomyosis: a systematic review. Hum Reprod Update. 2021;27:108-29.
  • Sfakianoudis K, Rapani A, Grigoriadis S, Pantou A, Maziotis E, Kokkini G et al. The role of uterine natural killer cells on recurrent miscarriage and recurrent implantation failure: from pathophysiology to treatment. Biomedicines. 2021;9:1425.
  • Chiu CSC, Yeh LY, Pan SH, Li SH. Transcriptomic analysis reveals intrinsic abnormalities in endometrial polyps. Int J Mol Sci. 2024;25:2557.
  • Dibi RP, Zettler CG, Vanin CMDM, Ribeiro RVP, Oliveira JMD, Kremer TG et al. Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study. Sao Paulo Med J. 2020;138:64-8.
  • Ryu KJ, Kim MS, Lee JY, Nam S, Jeong HG, Kim T et al. Risk of endometrial polyps, hyperplasia, carcinoma, and uterine cancer after tamoxifen treatment in premenopausal women with breast cancer. JAMA Netw Open. 2022;5:e2243951.
  • Mangla M, Palo S, Kanikaram PK, Raja Shekar P, Setty A. Comparative immuno-profiling of proliferative and disordered proliferative endometrium in anovulatory abnormal uterine bleeding. J Obstet Gynaecol Res. 2025;51:e70032.
  • Shivhare SB, Bulmer JN, Innes BA, Hapangama DK, Lash GE. Menstrual cycle distribution of uterine natural killer cells is altered in heavy menstrual bleeding. J Reprod Immunol. 2015;112:88-94
There are 29 citations in total.

Details

Primary Language English
Subjects Humoural Immunology and Immunochemistry
Journal Section Research Article
Authors

Tiinçe Aksak 0000-0001-7841-8456

Harika Topal Önal 0000-0002-7466-2942

Project Number no project number
Submission Date June 10, 2025
Acceptance Date September 25, 2025
Publication Date December 22, 2025
Published in Issue Year 2025 Volume: 50 Issue: 4

Cite

MLA Aksak, Tiinçe and Harika Topal Önal. “Molecular and Immunohistochemical Evaluation of CD56 Gene Expression and UNK Cell Percentage in Endometrial Polyps”. Cukurova Medical Journal, vol. 50, no. 4, 2025, pp. 964-71, doi:10.17826/cumj.1716574.