Characteristics of the expression level of E-Cadherin and ß-Catenin in hepatocellular and cholangiocellular liver carcinoma

Authors

  • M. D. Zubko

DOI:

https://doi.org/10.14739/2310-1237.2015.2.50816

Keywords:

Hepatocellular Carcinoma, Cholangiocellular Carcinoma, E-Cadherin, beta-Catenin

Abstract

Aim. In order to determine the level of immunohistochemical expression of E-cadherin and β-catenin in hepatocellular and cholangiocellular liver cancer of different diameters and areas of the immunopositive cells trephine biopsies of liver of 94 patients were studied, among them 55 (58.51%) had hepatocellular carcinoma (HCC) and 39 (41.49%) had cholangiocellular liver cancer (CCC).

Methods and results. Considering the size of the tumor determined by ultrasound examination of the liver 21 HCC and 17 CCC less than5 cmin diameter, and 34 HCC and 22 CCC with diameter more than 5 cm were assayed. The expression of E-cadherin by cells was determined using a monoclonal antibody Mo-Hu E -Cadherin, Clone NCH-38, and the expression of β-catenin - using monoclonal antibodies Mo a Hu Beta-Catenin, Clone E247 ß-Catenin-1. The level of expression of immunohistochemical markers of tumor cells and immunopositive tumor cells area were determined by photo digital  morphometry in digital image processing program Image J. It was found that in 63,64% of patients with HCC and 100% of patients with CCC, liver cancer cells show membrane or membrane-cytoplasmic expression of E-cadherin. E-cadherin immunopositive cells make up 42,25±15,12% of area of HCC tissue section and 35,13±15,69% of area of liver tissue section of CCC. In the 94,55% of HCC cases and 100% of patients with CCC membrane expression of β-catenin, combined with a nuclear or cytoplasmic expression of the protein, was revealed in tumor cells. β-catenin immunopositive cells make up 62,39±20,41% of area of HCC tissue section and 55,83±19,67% of area of liver tissue section in CCC. In HCC and CCC, between low expression of E-cadherin by tumor cells and high levels of β-catenin a direct strong correlation is observed. In large HCC and CCC compared with smaller tumors up to5 cmin diameter, significantly smaller space was occupied by E-cadherin-immunopositive cells and larger area was occupied by β-catenin-immunopositive cells.

Conclusion. The comparison of the expression of adhesively-migration markers by tumor cells shows that hepatocellular carcinoma and cholangiocellular cancer are characterized by early loss of intercellular adhesion bonds and high potencies to invasive growth in the liver.

References

Polishchuk, L. Z., Riabtseva, O. D., Luk’ianova, N. Yu., & Chekhun, V. F. (2011)

Molekuly adhezii ta yikh znachennia pry rozvytku zloiakisnykh pukhlyn [Adhesion molecules and their importance in the development of malignant tumors]. Onkolohiia, 13(1), 4–10. [in Ukrainian].

Kopnin, B. P. (2004) Opukholevye supressory i mutatornye geny [Tumor suppressor genes and the mutator]. Kancerogenez, (ed. D.G. Zaridze), (p. 125–157). Moscov: Medicina. [in Russian].

Van Aken, E., De Wever, O., Correia da Rocha, A. S., Mareel, M (2001) Defective E-cadherin/catenin complexes in human cancer. Virchows Arch., 439(6), 725–751. doi: 10.1007/s004280100516.

Jiang Chen, Jie Zhao, Rui Ma, Hui Lin, Xiao Liang, & Xiujun Cai (2014) Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma. PLoS One., 9(8), e103952. doi: 10.1371/journal.pone.0103952.

Lazarevich, N. L. (2004) Molekulyarnye mekhanizmy progressii opukholej pecheni [Molecular mechanisms of the progression of liver tumors]. Uspekhi biologicheskoj khimii, 44, 365–418. [in Russian].

Suzuki, T, Yano, H., Nakashima, Y., Nakashima, O., Kojiro, M. (2002) Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process. M. J Gastroenterol Hepatol, 17(9), 994–1000. doi: 10.1046/j.1440-1746.2002.02774.x.

Harada, N., Oshima, H., Katoh, M., Tamai, Y., Oshima, M., & Taketo, M. M. (2004) Hepatocarcinogenesis in mice with beta-catenin and Haras gene mutations. Cancer Res, 64(1), 48–54.

Nakagawa, H., Hikiba, Y., Hirata, Y., Font-Burgada, J., Sakamoto, K., Hayakawa, Y. (2014) Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis. Proc Natl Acad Sci U S A, 111(3), 1090–1095. doi: 10.1073/pnas.1322731111.

Rasband, W. S. (1997–2012) Image J, U. S. National Institutes of Health, Bethesda, Maryland, USA. Retrieved from http://imagej.nih.gov/ij/.

Singh Monga, S. P. (2015) β-Catenin Signaling and Roles in Liver Homeostasis, Injury And Tumorigenesis. Gastroenterology. doi: 10.1053/j.gastro.2015.02.056.

Boyault, S., Rickman, D. S., de Reyniès, A., Balabaud, C., Rebouissou, S., Jeannot, E., et al. (2007) Transcriptome classification ofHCC is related to gene alterations and to new therapeutic targets. Hepatology, 45(1), 42–52. doi: 10.1002/hep.21467.

Suzuki, T., Yano, H., Nakashima, Y., Nakashima, O., & Kojiro, M. (2002) Beta-catenin expression in hepatocellular carcinoma: a possible participation of beta-catenin in the dedifferentiation process. J Gastroenterol Hepatol, 17(9), 994–1000. doi: 10.1046/j.1440-1746.2002.02774.x.

Hoshida, Y., Nijman, S. M., Kobayashi, M., Chan, J. A., Brunet, J. P., Chiang, D. Y., et al. (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res, 69(18), 7385–7392. doi: 10.1158/0008-5472.CAN-09-1089.

Nejak-Bowen, K. N. & Monga, S. P. (2011) Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the good from the bad. Semin Cancer Biol., 21(1), 44–58. doi: 10.1016/j.semcancer.2010.12.010.

Peifeng, Li, Yongcheng, Cao, Yamin, Li, Luting, Zhou, Xiaohong, Liu, Ming, Geng (2014) Expression of Wnt-5a and β-catenin in primary hepatocellular carcinoma. Int J Clin Exp Pathol, 7(6), 3190–3195.

Tien, L. T., Ito, M., Nakao, M., Niino, D., Serik, M., Nakashima, M., et al. (2005) Expression of β-catenin in hepatocellular carcinoma. World J Gastroenterol, 11(16), 2398–2401.

Bae, S. H., Jung, E. S., Park, Y. M., Jang, J. W., Choi, J. Y., Cho, S. H., et al. (2002) Expression patterns of E-cadherin and beta-catenin according to clinicopathological characteristics of hepatocellular carcinoma. Taehan Kan Hakhoe Chi., 8(3), 297–303.

Settakorn, J., Kaewpila, N., Burns, G. F., & Leong, A S-Y. (2005) FAT, E-cadherin, β catenin, HER 2/neu, Ki67 immunoexpression, and histological grade in intrahepatic cholangiocarcinoma. J Clin Pathol., 58, 1249–1254. doi:10.1136/jcp.2005.026575.

Downloads

How to Cite

1.
Zubko MD. Characteristics of the expression level of E-Cadherin and ß-Catenin in hepatocellular and cholangiocellular liver carcinoma. Pathologia [Internet]. 2015Oct.8 [cited 2024Nov.23];(2). Available from: http://pat.zsmu.edu.ua/article/view/50816

Issue

No. 2 (2015)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Лицензия Creative Commons
    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

  1. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).