Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma

Authors

  • V. A. Tumanskiy Zaporizhzhia State Medical University,
  • A. V. Chepets Zaporizhzhia State Medical University,
  • А. М. Kamyshnyi Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2016.2.81328

Keywords:

Endometrial Neoplasms, Cadherins, beta Catenin, VEGFA protein, Human, Polymerase Chain Reaction, RNA, Messenger

Abstract

The violation of Wnt-signaling pathway and cyclic neoangiogenesis is early events in endometrial carcinogenesis. In this process an important role is played by epigenetic modifications and mutations of CDH1, CTNNB1, VEGFA genes, followed by expression violations of E-cadherin, β-catenin, VEGFA encoded by them.

The aim. To study the expression levels of mRNA of CDH1, CTNNB1, VEGFA genes and the expression levels of E-cadherin, β-catenin, VEGFA in non-metastatic endometrioid endometrial carcinoma (EEC) and in EEC with metastases to regional lymph nodes.

Materials and methods. Immunohistochemical study of invasive рТ1-4N0Mx endometrioid endometrial carcinoma (EEC) (n=56; age – 42–83 years), invasive рТ1-4N1-2Mx EEC (n=30; age – 48–79 years), samples of normal proliferative endometrium (PE) (n=30; age – 41–62 years) was performed. Molecular-genetic study of invasive рТ1-4N0Mx EEC (n=10; age – 45–67 years), invasive рТ1-4N1-2Mx EEC (n=10; age – 44–63 years), samples of PE (n=10; age – 46–59 years) was performed.

Results. EEC is characterized by the lower mRNA expression level of CDH1 gene and by the higher mRNA expression levels of CTNNB1, VEGFA genes in comparison with the PE. E-cadherin expression level is 32.6 % lower in non-metastatic EEC and also is 58.10 % lower in metastatic EEC in comparison with the PE. β-catenin expression level is 32.56 % lower in non-metastatic EEC and also is 58.11 % lower in metastatic EEC in comparison with the PE. VEGFA expression level is 27.72 % higher in non-metastatic EEC and also is 17.87 % higher in metastatic EEC in comparison with the PE. There is lower β-catenin expression level in metastatic EEC in comparison with non-metastatic EEC. Non-metastatic and metastatic EEC is characterized by the direct medium connections between the mRNA expression levels of CTNNB1 and VEGFA genes (γ=0.44), between the mRNA expression level of CTNNB1 gene and VEGFA expression level in the tumor (γ=0.37).

Conclusions. These changes contribute to tumor growth, invasion and metastasis. 

References

Gulyaeva, L. F., & Krasilnikov, S. E. (2012). Molekulyarnye mekhanizmy kancerogeneza e´ndometriya [Molecular mechanisms of endometrial carcinoma]. Byulleten' Vostochno-Sibirskogo nauchnogo centra Sibirskogo otdeleniya Rossijskoj akademii medicinskikh nauk, 3–1(85), 110–115. [in Russian].

Jia, Sh., Wei, Y., Liu, H., Fu, J., Wang, F., & Zhang, Y. (2015). Signaling pathway in endometrial carcinoma. Cancer Genetics and Epigenetics, 3(3), 1–4. doi: 10.5376/cge.2015.03.0003.

Ma, X., Ma, Ch. X., & Wang, J. (2014). Endometrial Carcinogenesis and Molecular Signaling Pathways. American Journal of Molecular Biology, 4, 134–149. doi: 10.4236/ajmb.2014.43015.

Nachajova, M., Mersakova, S., Sivakova, J., Krivus, S., Szepe, P., Hatok, J., & Adamkov, M. (2015). New molecular aspects of endometrial carcinoma. Neuroendocrinology Letters, 36(7), 638–643.

Llobet, D., Pallares, J., Yeramian, A., Santacana, M., Eritja, N., Velasco, A., et al. (2009). Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints. Journal of Clinical Pathology, 62(9), 777–785. doi: 10.1136/jcp.2008.056101.

Song, J. L., Nigam, P., Tektas, S. S., & Selva, E. (2015). МicroRNA regulation of Wnt signaling pathways in development and disease. CellularSignalling, 27, 1380–1391. doi: 10.1016/j.cellsig.2015.03.018.

Valenta, T., Hausmann, G., & Basler, K. (2012). The many faces and functions of β-catenin. The EMBO Journal, 31(12), 2714–2736. doi: 10.1038/emboj.2012.150.

Markowska, А., Pawałowska, М., Lubin, М., & Markowska, J. (2014). Signalling pathways in endometrial cancer. Contemporary oncology (Poznań, Poland), 18(3), 143–148. doi: 10.5114/wo.2014.43154.

Isaeva, A. V., Zima, A. P., Shabalova, I. P., Ryazantseva, N. V., Vasil´eva, O. A., Kasoyan, K. T., et al. (2015) β-katenin: struktura, funkcii i rol' v opukholevoj transformacii e´pitelial'nykh kletok [SS-catenin: structure, function and role in malignant transformation of epithelial cells]. Vestnik RAMN, 4(70), 475–483. [in Russian].

Prat, J., Gallardo, A., Cuatrecasas, M., & Catasus, L. (2007). Endometrial carcinoma: pathology and genetics. Pathology, 39, 72–87. doi: 10.1080/00313020601136153.

Yuzhou, Z., Kangdong, L., Minxia, D. U., Chunyang, L. I., & Ziming, D. (2013). Expression of E-cadherin, β-catenin and uPA proteins in endometrial carcinoma and their clinical significance mechanism. Life Science Journal, 10(2), 2915–2919.

Dobrzycka, B., Terlikowski, S. J., Kwiatkowski, M., Garbowicz, M., Kinalski, M., & Chyczewski, L. (2010). Prognostic significance of VEGF and its receptors in endometrioid endometrial cancer. Ginekologia Polska, 81, 422–425.

Dabbs, D. J. (Ed.) (2010). Diagnostic Immunohistochemistry. Philadelphia: Saunders/Elsevier.

Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent Ukrainy na korysnu model № 99314 Ukraina, MPK (2015) G01N 21/00, G06K 9/00. Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ [Ukraine patent for utility model №99314 Ukraine, IPC (2015) G01N 21/00, G06K 9/00. Method of photo digital morphometrical study of immunohistochemical micropreparations]. Biuleten, 10. [in Ukrainian].

Rasband, W. S. (1997–2016) Image. J. Bethesda, Maryland. Retrived from: http://imagej.nih.gov/ij/

Tumanskiy, V. A., & Chepets, A. V. (2015). Immunogistokhimicheskaya ocenka e´kspressii molekul kletochnoj adgezii E-kadgerina i β-katenina kletkami e´ndometrioidnoj adenokarcinomy e´ndometriya [Immunohistochemical characterization of the expression of cell adhesion molecules E-cadherin and β-catenin in the invasive endometrioid endometrial carcinoma]. Pathologia, 2, 75–80. doi: http://dx.doi.org/10.14739/2310-1237.2015.2.50871.

Chernobrovkina, A. E., & Svirin, N. A. (2014) Rak e´ndometriya: geterogennost' i geneticheskie markery [Endometrial Cancer: heterogeneity and genetic markers]. MEDLINE.RU, 15(3), 649–671. Retrived from: http://www.medline.ru/. [in Russian].

Yi, T. Z., Guo, J., Zhou, L., Chen, X., Mi, R. R., Qu, Q. X., et al. (2011). Prognostic value of E-cadherin expression and CDH1 promoter methylation in patients with endometrial carcinoma. Cancer Investigation, 29(1), 86–92. doi: 10.3109/07357907.2010.512603.

Van der Horst, P. H., Wang, Y., Vandenput, I., Kühne, L. C., Ewing, P. C., van Ijcken, W. F. J., et al. (2012). Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer. PLoS ONE, 7(1), e30840. doi: 10.1371/journal.pone.0030840.

van der Zee, M., Jia, Y., Wang, Y., Heijmans-Antonissen, C., Ewing, P. C., Franken, P., et al. (2013). Alterations in Wnt-β-catenin and Ptensignalling play distinct roles in endometrial cancer initiation and progression. The Journal of Pathology, 230, 48–58. doi: 10.1002/path.4160.

Dobrzycka, B., & Terlikowski, S. J. (2010). Biomarkers as prognostic factors in endometrial cancer. Folia histochemica et cytobiologica, 48(3), 319–322. doi: 10.2478/v10042-10-0061-8.

Kiewisz, J., Wasniewski, T., & Kmiec, Z. (2015). Participation of WNT and β-Catenin in Physiological and Pathological Endometrial Changes: Association with Angiogenesis. Biomed Research International, 2015, doi: 10.1155/2015/854056.

Downloads

How to Cite

1.
Tumanskiy VA, Chepets AV, Kamyshnyi АМ. Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma. Pathologia [Internet]. 2016Oct.27 [cited 2024Apr.21];13(2). Available from: http://pat.zsmu.edu.ua/article/view/81328

Issue

Section

Original research