Epithelial-mesenchymal transition in сolorectal adenocarcinoma progression

Authors

  • M. A. Shyshkin Zaporizhzhіa State Medical University, Ukraine,
  • S. V. Fen Zaporizhzhіa State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2020.5.214747

Keywords:

сolorectal сancer, E-cadherin, cytokeratin 20, alpha-SMA protein, vimentin, epithelial-mesenchymal transition

Abstract

 

Aim – to analyze immunohistochemical expression levels of epithelial and mesenchymal phenotype markers in colorectal adenocarcinoma on I–IV stages (pTNM).

Materials and methods. Pathohistological and immunohistochemical studies of surgical material from 30 patients that had undergone surgical treatment of colorectal adenocarcinoma (I–IV stages) were carried out.

Results. Colorectal adenocarcinoma is characterized by the low E-cadherin expression level is 45.94 (32.04; 58.26) CUOD. A statistically significant decrease in the marker expression level in sequence from stages I to IV was revealed. Carcinoma is characterized by the medium CK-20 expression level is 54.28 (41.55; 70.27) CUOD. A statistically significant decrease in the marker expression level in the studied sequence was revealed as well. Furthermore, CK-20 expression is revealed not only in cancer cells clusters, but also in cells which are located separately in tumor stroma. Colorectal adenocarcinoma is characterized by the medium vimentin expression level in the stroma is 95.23 (80.22; 110.21) CUOD. A statistically significant increase in the marker expression level in sequence from stages I to IV was revealed. Besides, there is a tendency to vimentin-immunopositive cells accumulation near cancer cells clusters. Carcinoma is characterized by the medium α-SMA expression level: the median of its expression is 75.71 (60.22; 90.34) CUOD. There is also a tendency to α-SMA-immunopositive cells accumulation near cancer cells clusters. Correlation analysis revealed direct connections between E-cadherin and CK-20 expression levels (r = 0.74, P ˂ 0.05), vimentin and α-SMA expression levels (r = 0.53, P ˂ 0.05). Moreover, reverse connections between E-cadherin and vimentin expression levels (r = -0.43, P ˂ 0.05), E-cadherin and α-SMA expression levels (r = -0.53, P ˂ 0.05), CK-20 and vimentin expression levels (r = -0.65, P ˂ 0.05), CK-20 and α-SMA expression levels (r = -0.69, P ˂ 0.05) were revealed.

Conclusions. Parallel loss of epithelial phenotype and an increase of mesenchymal phenotype cells number occur during colorectal adenocarcinoma progression from stages I to IV (pTNM).

 

References

Rawla, P., Sunkara, T., & Barsouk, A. (2019). Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Przeglad Gastroenterologiczny, 14(2), 89-103. https://doi.org/10.5114/pg.2018.81072

Church, J. (2016). Molecular genetics of colorectal cancer. Seminars in Colon and Rectal Surgery, 27(4), 172-175. https://doi.org/10.1053/j.scrs.2016.04.013

Illam, S. P., Narayanankutty, A., Mathew, S. E., Valsalakumari, R., Jacob, R. M., & Raghavamenon, A. C. (2017). Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals. Recent Patents on Anti-Cancer Drug Discovery, 12(3), 234-246. https://doi.org/10.2174/1574892812666170424150407

Vu, T., & Datta, P. K. (2017). Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis. Cancers, 9(12), Article 171. https://doi.org/10.3390/cancers9120171

Zhu, Q. C., Gao, R. Y., Wu, W., & Qin, H. L. (2013). Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer. Asian Pacific Journal of Cancer Prevention, 14(5), 2689-2698. https://doi.org/10.7314/apjcp.2013.14.5.2689

Wong, S., Fang, C. M., Chuah, L. H., Leong, C. O., & Ngai, S. C. (2018). E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Critical Reviews in Oncology/Hematology, 121, 11-22. https://doi.org/10.1016/j.critrevonc.2017.11.010

Dmello, C., Srivastava, S. S., Tiwari, R., Chaudhari, P.R., Sawant, S., & Vaidya, M. M. (2019). Multifaceted role of keratins in epithelial cell differentiation and transformation. Journal of Biosciences, 44(2), Article 33. https://doi.org/10.1007/s12038-019-9864-8

Al-Maghrabi, J., Emam, E., & Gomaa, W. (2018). Immunohistochemical staining of cytokeratin 20 and cytokeratin 7 in colorectal carcinomas: Four different immunostaining profiles. Saudi Journal of Gastroenterology, 24(2), 129-134. https://doi.org/10.4103/sjg.SJG_465_17

Battaglia, R. A., Delic, S., Herrmann, H., & Snider, N. T. (2018). Vimentin on the move: new developments in cell migration. F1000Research, 7(F1000 Faculty Rev), Article 1796. https://doi.org/10.12688/f1000research.15967.1

Ribatti, D., Tamma, R., & Annese, T. (2020). Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Translational Oncology, 13(6), Article 100773. https://doi.org/10.1016/j.tranon.2020.100773

Kuzet, S. E., & Gaggioli, C. (2016). Fibroblast activation in cancer: when seed fertilizes soil. Cell and Tissue Research, 365(3), 607-619. https://doi.org/10.1007/s00441-016-2467-x

Schatoff, E. M., Leach, B. I., & Dow, L. E. (2017). Wnt Signaling and Colorectal Cancer. Current Colorectal Cancer Reports, 13(2), 101-110. https://doi.org/10.1007/s11888-017-0354-9

Fei, F., Li, C., Cao, Y., Liu, K., Du, J., Gu, Y., Wang, X., Li, Y., & Zhang, S. (2019). CK7 expression associates with the location, differentiation, lymph node metastasis, and the Dukes' stage of primary colorectal cancers. Journal of Cancer, 10(11), 2510-2519. https://doi.org/10.7150/jca.29397

Lyn, J., Wang, Y., Wang, F., Shen, M., & Zhou, X. (2015). Diagnostic value of SATB2, CK7 and CK20 in colorectal cancer. Zhonghua Bing Li Xue Za Zhi, 44(8), 578-581.

Danielsson, F., Peterson, M. K., Caldeira Araújo, H., Lautenschläger, F., & Gad, A. (2018). Vimentin Diversity in Health and Disease. Cells, 7(10), Article 147. https://doi.org/10.3390/cells7100147

McDonald-Hyman, C., Muller, J. T., Loschi, M., Thangavelu, G., Saha, A., Kumari, S., Reichenbach, D. K., Smith, M. J., Zhang, G., Koehn, B. H., Lin, J., Mitchell, J. S., Fife, B. T., Panoskaltsis-Mortari, A., Feser, C. J., Kirchmeier, A. K., Osborn, M. J., Hippen, K. L., Kelekar, A., Serody, J. S., … Blazar, B. R. (2018). The vimentin intermediate filament network restrains regulatory T cell suppression of graft-versus-host disease. The Journal of Clinical Investigation, 128(10), 4604-4621. https://doi.org/10.1172/JCI95713

Toiyama, Y., Yasuda, H., Saigusa, S., Tanaka, K., Inoue, Y., Goel, A., & Kusunoki, M. (2013). Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. Carcinogenesis, 34(11), 2548-2557. https://doi.org/10.1093/carcin/bgt282

Meyer, S. N., Galván, J. A., Zahnd, S., Sokol, L., Dawson, H., Lugli, A., & Zlobec, I. (2019). Co-expression of cytokeratin and vimentin in colorectal cancer highlights a subset of tumor buds and an atypical cancer-associated stroma. Human Pathology, 87, 18-27. https://doi.org/10.1016/j.humpath.2019.02.002

Son, G. M., Kwon, M. S., Shin, D. H., Shin, N., Ryu, D., & Kang, C. D. (2019). Comparisons of cancer-associated fibroblasts in the intratumoral stroma and invasive front in colorectal cancer. Medicine, 98(18), Article e15164. https://doi.org/10.1097/MD.0000000000015164

Hanley, C. J., Noble, F., Ward, M., Bullock, M., Drifka, C., Mellone, M., Manousopoulou, A., Johnston, H. E., Hayden, A., Thirdborough, S., Liu, Y., Smith, D. M., Mellows, T., Kao, W. J., Garbis, S. D., Mirnezami, A., Underwood, T. J., Eliceiri, K. W., & Thomas, G. J. (2016). A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers. Oncotarget, 7(5), 6159-6174. https://doi.org/10.18632/oncotarget.6740

Kalluri, R. (2016). The biology and function of fibroblasts in cancer. Nature Reviews Cancer, 16(9), 582-598. https://doi.org/10.1038/nrc.2016.73

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1.
Shyshkin MA, Fen SV. Epithelial-mesenchymal transition in сolorectal adenocarcinoma progression. Zaporozhye Medical Journal [Internet]. 2020Oct.20 [cited 2024Dec.26];22(5). Available from: http://zmj.zsmu.edu.ua/article/view/214747

Issue

Vol. 22 No. 5 (2020)

Section

Original research

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