Analysis of proliferation and apoptosis, MUC-1 and Cdx-2 expression in distal colonic polyps

Authors

  • M. A. Shyshkin Zaporizhzhіa State Medical University, Zaporizhzhіa, Ukraine, Ukraine
  • T. A. Khrystenko Zaporizhzhіa State Medical University, Zaporizhzhіa, Ukraine, Ukraine https://orcid.org/0000-0003-3364-3339

DOI:

https://doi.org/10.26641/1997-9665.2020.3.124-131

Keywords:

intestinal neoplasms, polyps, cell proliferation, apoptosis, mucins, cdx2 transcription factor

Abstract

Background. The universal molecular characteristics of malignancy are activation of cell proliferation and inactivation of apoptotic cell death. Besides genes-regulators of the processes other molecules are involved, including mucins and Cdx-2. Aim. To conduct comparative and correlation analysis of indexes of immunohistochemical expression of Ki-67, p53, caspase-3, as well as MUC-1 and Cdx-2 in distal colonic polyps. Methods. Pathohistological and immunohistochemical studies of biopsies of adenomas and hyperplastic polyps from 40 patients were carried out. Results. Distal colonic polyps are characterized by medium proliferation level: the median of Ki-67 expression for hyperplastic polyps is 42,20 (35,27; 52,38) %, while the median for adenomas is 65,39 (52,28; 76,23) % (р˂0,05). The polyps are characterized by low p53 expression levels: the median of the marker expression for hyperplastic polyps is 1,53 (1,17; 3,16) %, for adenomas – 9,15 (8,26; 12,39) % (р˂0,05). The studied polyps are characterized by low apoptosis levels: the median of caspase-3 expression for hyperplastic polyps is 33,78 (30,28; 42,34) CUOD, for adenomas – 22,19 (16,84; 40,51) CUOD (р˂0,05). Distal colonic polyps are characterized by medium MUC-1 and Cdx-2 expression levels: the medians of the markers expression for hyperplastic polyps are 62,13 (34,20; 71,85) CUOD and 71,81 (62,36; 77,77) CUOD, for adenomas – 80,25 (52,14; 95,21) CUOD and 95,14 (81,19; 112,17) CUOD, respectively (р˂0,05). The correlation analysis revealed several correlations: reverse medium strength correlation between p53 and caspase-3 expression levels (r = -0,57, р˂0,05), direct medium strength correlation between caspase-3 and MUC-1 expression levels (r = 0,52, p˂0,05) take place in hyperplastic polyps, whereas reverse strong correlation between caspase-3 and MUC-1 expression levels 1 (r = -0,88, p˂0,05) takes place in adenomas. Conclusions. Distal colonic adenomas differ by higher proliferation and p53 expression levels, comparing to hyperplastic polyps, and by lower apoptosis level that is associated with higher MUC-1 expression level as well. Hyperplastic polyps differ by higher apoptosis level that is associated with lower MUC-1 expression level. Cdx-2 expression increases on benign adenoma stage and does not correlate with proliferation and apoptosis indexes.

References

  1. Singh R, Tao Pu LС, Koay D, Burt A. Sessile serrated adenoma/polyps: Where are we at in 2016? World Journal of Gastroenterology. 2016;22(34):7754-59.
  2. Cekodhima G, Cekodhima A, Beqiri A, Alimehmeti M, & Sulo G. Demographic and histopathological characteristics of colorectal polyps: a descriptive study based on samples obtained from symptomatic patients. Slovenian Journal of Public Health. 2016;55(2): 118-123.
  3. WHO Classification of Tumours. Digestive System Tumours. 5th ed. Lyon, 2019. P. 158.
  4. Jan R, Chaudhry GE. Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics. Advanced pharmaceutical bulletin. 2019;9(2):205–218. https://doi.org/10.15171/apb.2019.024
  5. Betge J, Schneider NI, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, Ebert MP, Langner C. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Archiv: an international journal of pathology. 2016;469(3):255-265.
  6. Li C, Zuo D, Liu T, Yin L, Li C. Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis. Gastroenterology Research and Practice. 2019; 16. https://doi.org/10.1155/2019/2391670
  7. Chawehgsaksophak K. Cdx2 Animal Models Reveal Developmental Origins of Cancers. Genes. 2019;10(11):928. https://doi.org/10.3390/genes10110928
  8. Hryniuk A, Grainger S, Savory JGA, Johnes D. Cdx1 and Cdx2 Function as Tumor Suppressors. Journal of Biological Chemistry. 2014;289:33343-33354. https://doi.org/10.1074/jbc.M114.583823
  9. Graule J, Uth K, Fischer E, Centeno I, Galvan JA, Eichmann M, Rau TT, Langer R, Dawson H, Nitsche U, Traeger P, Zlobec I. CDX2 in colorectal cancer is an independent prognostic factor and regulated by promoter methylation and histone deacetylation in tumors of the serrated pathway. Clinical Epigenetics. 2018;10. https://doi.org/10.1186/s13148-018-0548-2
  10. Wang Y, Li Z, Li W, Liu S, Han B. Methylation of promoter region of CDX2 gene in colorectal cancer. Oncology Letters. 2016;12(5):3229-3233. https://doi.org/10.3892/ol.2016.5109
  11. Nusse R, Clevers H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell. 2017;169(6):985–989. https://doi.org/10.1016/j.cell.2017.05.016
  12. Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell. 2017;170(6):1062–1078. https://doi.org/10.1016/j.cell.2017.08.028
  13. Julien O, Wells JA. Caspases and their substrates. Cell death and differentiation. 2017;24(8):1380–1389. https://doi.org/10.1038/cdd.2017.44

Downloads

How to Cite

Shyshkin, M. A., & Khrystenko, T. A. (2020). Analysis of proliferation and apoptosis, MUC-1 and Cdx-2 expression in distal colonic polyps. Морфологія / Morphologia / Morfologìâ, 14(3), 124–131. https://doi.org/10.26641/1997-9665.2020.3.124-131

Issue

Vol. 14 No. 3 (2020)

Section

Статті

License

Copyright (c) 2020 Morphologia

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

 The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.
        By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world. 
        The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.