Immunohistochemical markers of the activity of apoptosis and proliferation in women with adenomyosis who had papillary thyroid carcinoma

and methods. 63 women of reproductive age were examined: group I – 31 patients with adenomyosis and PTC in history, group II – 32 patients with adenomyosis and normal thyroid status. The intensity of pelvic pain was assessed using a visual analog scale in all women. The material for morphological research was obtained with Pipelle biopsy of the endometrium in the secretory phase of the menstrual cycle. A morphological study was performed on 30 biopsies of eutopic endometrium (15 samples from patients of group I and 15 samples from patients of group II). An immunohistochemical study was performed using monoclonal antibodies to cell-specific markers Bcl-2 (DAKO, clone 124) and Ki-67 (DAKO, clone MIB-1). Results. High expression of Bcl-2 was detected in the endometrial glandular epithelial cells (EGECs) in 70% and 62.5% of samples in group I and II respectively (р > 0.05), the number of Bcl-2-positive cells was significantly higher in samples from group I (80.0 ± 13.1% versus 60.0 ± 15.2% in group І and ІІ respectively, р 0.05), no significant difference in the number of positive cells was found between groups (18.9 ± 12.2% and 12.6 ± 9.1% in group І and ІІ respectively, р > 0.05). Expression of Ki-67 was detected in the EGECs in 70% and 62.5% (р > 0.05) of samples in group І and ІІ respectively and in the ESCs in 100% of samples from groups I and II respectively. The immunocytochemical Ki-67 labelling index was much more prominent in group I (45.0 ± 11.4% versus 25.8 ± 16.7% EGECs (р < 0.05); 26.5 ± 10.2% versus 16.3 ± 8.9% ESCs (р < 0.05) for group I and II respectively). Conclusions. Altered proliferation of the eutopic endometrium with marked resistance to apoptosis was found in reproductive aged female with adenomyosis and PTC in history, that is can be considered as a marker of the aggressiveness of the disease course in this cohort of patients.

- Stratopoulou, C.A., Donnez, J., Dolmans, M.M. “Origin and Pathogenic Mechanisms of Uterine Adenomyosis: What Is Known So Far.” Reprod Sci 28 (2021): 2087–97. - García-Solares, J., Donnez, J., Donnez, O., Dolmans, M.-M. “Pathogenesis of uterine adenomyosis: invagination or metaplasia?” Fertil Steril 109.3 (2018): 371–9. DOI: 10.1016/j.fertnstert.2017.12.030 - Chapron, C., Vannuccini, S., Santulli, P., et al. “Diagnosing adenomyosis: An integrated clinical and imaging approach.” Hum Reprod Update 26.3 (2020): 392–411. - Patel, B.G., Rudnicki, M., Yu, J., et al. “Progesterone resistance in endometriosis: origins, consequences and interventions.” Acta Obstet Gynecol Scand 96.6 (2017): 623–32. - Alcalde, A.M., Martínez-Zamora, M.Á., Gracia, M., et al. “Impact of Adenomyosis on Women’s Psychological Health and Work Productivity: A Comparative Cross-Sectional Study.” J Womens Health 30.11 (2021): 1653–9. Available from: [https://www.liebertpub.com/doi/abs/10.1089/jwh.2020.8789], last accessed Jan 5, 2022. - Alcalde, A.M., Martínez-Zamora, M.Á., Gracia, M., et al. “Assessment of Quality of Life, Sexual Quality of Life, and Pain Symptoms in Deep Infiltrating Endometriosis Patients With or Without Associated Adenomyosis and the Influence of a Flexible Extended Combined Oral Contraceptive Regimen: Results of a Prospective, Observational Study.” J Sex Med 19.2 (2022): 311–8. - Danylova, A.O. “Quality of women’s life of with adenomyosis and papillary thyroid carcinoma in anamnesis.” Women’s Reproductive Health 1 (2022): 63–8. Available from: [http://repro-health.com.ua/article/view/258143]. - Ballard, K., Lowton, K., Wright, J. “What’s the delay? A qualitative study of women’s experiences of reaching a diagnosis of endometriosis.” Fertil Steril 86.5 (2006): 1296–301. - Danylova, A., Tatarchuk, T., Kalugina, L., Kuchmenko, T. “Hyperproliferative pathology of the reproductive system among female thyroid cancer survivors.” Eur J Obstet Gynecol Reprod Biol 270 (2022): e33. Available from: [http://www.ejog.org/article/S0301211521006771/fulltext]. - Zhu, X., Bai, Q., Lu, Y., et al. “Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer.” Int J Oncol 48.6 (2016): 2321–9. Available from: [http://www.spandidos- publications.com/10.3892/ijo.2016.3485/abstract]. - Xie, X., Shi, X., Guan, H., et al. “P21-activated kinase 4 involves TSH induced papillary thyroid cancer cell proliferation.” Oncotarget 8.15 (2017): 24882–91. Available from: [https://www.oncotarget.com/article/15079/text/]. - Li, J., Yin, G., Chen, M., et al. “Expression of CXCL12 and its receptor CXCR4 in patients with adenomyosis.” Oncol Lett 13.4 (2017): 2731–6. Available from: [http://www.spandidos-publications.com/10.3892/ol.2017.5762/abstract]. - Yi, K.W., Kim, S.H., Ihm, H.J., et al. “Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells.” Fertil Steril 103.4 (2015): 1089–97.e2. Available from: [http://dx.doi.org/10.1016/j.fertnstert.2014.12.124]. - Peyneau, M., Kavian, N., Chouzenoux, S., et al. “Role of thyroid dysimmunity and thyroid hormones in endometriosis.” Proc Natl Acad Sci 116.24 (2019): 11894–9. Available from: [http://www.pnas.org/lookup/doi/10.1073/pnas.1820469116]. - Danylova, A.O., Kalugina, L.V., Koseі, N.V., et al. “Peculiarities of hormonal homeostasis and endometrial receptor apparatus in women with adenomyosis, who suffered from papillary carcinoma of the thyroid gland.” Reprod Endocrinol 3.65 (2022): 101–6. Available from: [http://reproduct-endo.com/article/view/265141/261171]. - Oehler, M.K., Greschik, H., Fischer, D.C., et al. “Functional characterization of somatic point mutations of the human estrogen receptor α (hERα) in adenomyosis uteri.” Mol Hum Reprod 10.12 (2004): 853–60. Available from: [https://academic.oup.com/molehr/article/10/12/853/1020616]. - Yang, H.L., Chang, K.K., Mei, J., et al. “Estrogen restricts the apoptosis of endometrial stromal cells by promoting TSLP secretion.” Mol Med Rep 18.5 (2018): 4410–6. - Van den Bosch, T., Dueholm, M., Leone, F.P.G., et al. “Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: A consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.” Ultrasound Obstet Gynecol 46.3 (2015): 284–98. - Harmsen, M.J., Van den Bosch, T., de Leeuw, R.A., et al. “Consensus on revised definitions of morphological uterus sonographic assessment (MUSA) features of adenomyosis: results of a modified Delphi procedure.” Ultrasound Obstet Gynecol 2021 Sep 29. Available from: [https://onlinelibrary.wiley.com/doi/full/10.1002/uog.24786], last accessed May 25, 2022. - Yen, C.F., Huang, S.J., Lee, C.L., et al. “Molecular Characteristics of the Endometrium in Uterine Adenomyosis and Its Biochemical Microenvironment.” Reprod Sci 24.10 (2017): 1346–61. - Zahid, M., Goldner, W., Beseler, C.L., et al. “Unbalanced estrogen metabolism in thyroid cancer.” Int J Cancer 133.11 (2013): 2642–9. - Hopwood, D., Levison, D.A. “Atrophy and apoptosis in the cyclical human endometrium.” J Pathol 119.3 (1976): 159–66. - Yang, J.H., Wu, M.Y., Chen, C.D., et al. “Altered apoptosis and proliferation in endometrial stromal cells of women with adenomyosis.” Hum Reprod 22.4 (2007): 945–52. - Takagi-Morishita, Y., Yamada, N., Sugihara, A., et al. “Mouse uterine epithelial apoptosis is associated with expression of mitochondrial voltage-dependent anion channels, release of cytochrome C from mitochondria, and the ratio of Bax to Bcl-2 or Bcl-X.” Biol Reprod 68.4 (2003): 1178–84. - Mertens, H.J., Heineman, M.J., Evers, J.L. “The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of ovulatory menstrual cycles.” Gynecol Obstet Invest 53.4 (2002): 224–30. - Li, J., Yanyan, M., Mu, L., et al. “The expression of Bcl-2 in adenomyosis and its effect on proliferation, migration, and apoptosis of endometrial stromal cells.” Pathol Res Pract 215.8 (2019): 152477. - Li, B., Wang, L., Fan, Y., et al. “Expression and significance of bcl-2, bax and ER in foci of adenomyosis.” Zhonghua Fu Chan Ke Za Zhi 47.12 (2012): 923–7. - Fouqué, A., Lepvrier, E., Debure, L., et al. “The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria.” Cell Death Differ 23.10 (2016): 1702–16. Available from: [https://www.nature.com/articles/cdd201661]. - Wick, W., Wagner, S., Kerkau, S., et al. “BCL-2 promotes migration and invasiveness of human glioma cells.” FEBS Lett 440.3 (1998): 419–24. - Miller, I., Min, M., Yang, C., et al. “Ki67 is a Graded Rather than a Binary Marker of Proliferation versus Quiescence.” Cell Rep 24.5 (2018): 1105-1112.e5. Downloads Published How to Cite Issue Section License Copyright (c) 2023 М.Д. Тронько, А.О. Данилова, Л.В. Калугіна, Н.В. Косей, Т.М. Кучменко, Ю.М. Бондаренко This work is licensed under a Creative Commons Attribution 4.0 International License. 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