ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 14 of 61
Up
УЖМБС 2019, 4(5): 96–101
https://doi.org/10.26693/jmbs04.05.096
Experimental Medicine and Morphology

Immunohistochemical Features and Staging of Epithelial-Mesenchymal Transformation in Non-Muscle Invasive Bladder Cancer as the Criteria for Predicting Recurrence and Progression of the Disease

Yakovtsova I. I., Tytov Ye. V., Ivakhno I. V.
Abstract

Epithelial-mesenchymal transformation is the hallmark of the aggressive clinical behavior in cancers of different localization. It is well known that еpithelial-mesenchymal transformation is characterized by different degree, but the findings of the gradation of еpithelial-mesenchymal transformation in the scientific literature are practically absent. The purpose of the study was to investigate the immunohistochemical markers of еpithelial-mesenchymal transformation, considered as an aggregate, with identification it stage, as the criteria for recurrence and progression of the non-invasive urothelial bladder cancer. Material and methods. Non-invasive urothelial bladder cancers were divided into three groups by 14 cases for each group: group I – cancers without recurrence, group II – cases with recurrence without progression, and group III – cases with recurrence and progression. The immunohistochemical research was performed with application of E-cadherin, N-cadherin, vimentin, cytokeratins 7 and 20 monoclonal antibodies. Non-invasive urothelial bladder cancer on the degree of еpithelial-mesenchymal transformation was divided into 6 categories: 1) cancers without еpithelial-mesenchymal transformation (not expressing mesenchymal markers); 2) cancers with signs of еpithelial-mesenchymal transformation, predominantly epithelial phenotype (expression of epithelial markers was dominant over the expression of mesenchymal, p<0.05); 3) cancers with intermediate epithelial phenotype (expression of epithelial markers was dominant over the expression of mesenchymal, p>0.05); 4) cancers with intermediate mesenchymal phenotype; 5) cancers with a predominantly mesenchymal phenotype; 6) cancers with mesenchymal phenotype. Results and discussion. Expression of markers of the mesenchymal phenotype (vimentin and N-cadherin) was observed in 45.2% (19/42) of non-invasive urothelial bladder cancers. The appearance of еpithelial-mesenchymal transformation was associated with recurrence of the tumor (p<0.03). However, investigated markers of еpithelial-mesenchymal transformation variorum did not demonstrate statistical significance of belonging to any groups of research, so they cannot serve the criteria for recurrence or recurrence with progression of non-invasive urothelial bladder cancers. After distribution of еpithelial-mesenchymal transformation in two stages, it was revealed that non-invasive urothelial bladder cancers with recurrence were associated with the 1st stage of еpithelial-mesenchymal transformation (cancers with predominantly epithelial phenotype) (p<0.03), non-invasive urothelial bladder cancers with recurrence and progression were associated with the 2nd stage of еpithelial-mesenchymal transformation (cancers with intermediate epithelial phenotype) (p<0.05). Conclusion. Thus, staging of еpithelial-mesenchymal transformation with calculation of markers in conjunction is the valuable prognostic criteria for non-invasive urothelial bladder cancers.

Keywords: epithelial-mesenchymal transformation, non-invasive urothelial bladder cancer

Full text: PDF (Rus) 230K

References
  1. Balci MG, Tayfur M. Loss of E-cadherin expression in recurrent non-invasive urothelial carcinoma of the bladder. Int J Clin Exp Pathol. 2018; 11(8): 4163–8.
  2. Battaglia RA, Delic S, Herrmann H, Snider NT. Vimentin on the move: new developments in cell migration. F1000Research. 2018, 7: 1796. https://www.ncbi.nlm.nih.gov/pubmed/30505430. https://www.ncbi.nlm.nih.gov/pmc/articles/6241562. https://doi.org/10.12688/f1000research.15967.1
  3. Baumgart E, Cohen MS, Silva Neto B, Jacobs MA, Wotkowicz C, Rieger-Christ KM, et al. Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clinical Cancer Research. 2007; 13: 1685–94. https://www.ncbi.nlm.nih.gov/pubmed/17363521. https://doi.org/10.1158/1078-0432.CCR-06-2330
  4. Bostwick DG, Cheng L. Urologic Surgical Pathology, 3th edition. Philadelphia: USA: ELSEVIER Sanders; 2014. 1273 p.
  5. Bryan RT. 2015 Cell adhesion and urothelial bladder cancer: the role of cadherin switching and related phenomena. Philos Trans R Soc Lond B Biol Sci. 2015 Feb 5; 370(1661): 20140042. https://www.ncbi.nlm.nih.gov/pubmed/25533099. https://www.ncbi.nlm.nih.gov/pmc/articles/4275911. https://doi.org/10.1098/rstb.2014.0042
  6. Choi W, Czerniak B, Ochoa A, Su X, Siefker-Radtke A, Dinney C, et al. Intrinsic basal and Iuminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol. 2014; 11: 400-10. https://www.ncbi.nlm.nih.gov/pubmed/24960601. https://doi.org/10.1038/nrurol.2014.129
  7. Ghaini MH, Esmailneijad SS, Davati A. Cytokeratin 20 in Transitional Cell Carcinoma of Bladder and Its Relation with Prognostic Factors. Iranian J of Pathology. 2012; 7(3): 145–50.
  8. Gupta S, Cheville J, Hansel D. 218 Modeling E-Cadherin Expression Status to Predict Bladder Cancer Progression. American Journal of Clinical Pathology. 2018; 149(1): S93. https://doi.org/10.1093/ajcp/aqx123.217
  9. Hammam O, Wishahiz M, Khalil H, El Ganzouri H, Badawy M, Elkhquly A, et al. Expression of cytokeratin 7, 20, 14 in urothelial carcinoma and squamous cell carcinoma of the Egyprian urinary bladder cancer. J Egypt Soc Parasitol. 2014; 44(3): 733–40. https://www.ncbi.nlm.nih.gov/pubmed/25643514. https://doi.org/10.12816/0007876
  10. Hänze J, Henrici M, Hegele A, Hofmann R, Olbert PJ. Epithelial mesenchymal transition status is associated with anti-cancer responses towards receptor tyrosine-kinase inhibition by dovitinib in human bladder cancer cells. BMC Cancer. 2013; 13: 589. https://www.ncbi.nlm.nih.gov/pubmed/24325461. https://www.ncbi.nlm.nih.gov/pmc/articles/3866461. https://doi.org/10.1186/1471-2407-13-589
  11. Markiewicz A, Topa J, Nagel A, Skokowski J, Seroczynska B, Stokowy T, et al. Spectrum of Epithelial-Mesenchymal Transition Phenotypes in Circulating Tumour Cells from Early Breast Cancer Patients. Cancers (Basel). 2019 Jan 9; 11(1): pii: E59. https://www.ncbi.nlm.nih.gov/pubmed/30634453. https://www.ncbi.nlm.nih.gov/pmc/articles/6356662. https://doi.org/10.3390/cancers11010059
  12. Monteiro-Reis S, Lobo J, Henrique R, Jerónimo C. Epigenetic Mechanisms Influencing Epithelial to Mesenchymal Transition in Bladder Cancer. Int J Mol Sci. 2019; 20(297): pii: E297. https://www.ncbi.nlm.nih.gov/pubmed/30642115. https://www.ncbi.nlm.nih.gov/pmc/articles/6358899. https://doi.org/10.3390/ijms20020297
  13. Paliwa P, Arora D, Mishra AK. Epithelial mesenchymal transition in urothelial carcinoma: twist in the tale. Indian J Pathol Microbiol. 2012 Oct-Dec; 55(4): 443-9. https://www.ncbi.nlm.nih.gov/pubmed/23455777. https://doi.org/10.4103/0377-4929.107777
  14. Rahmani AH, Babiker AY, Alwanian WM, Elsiddig SA, Faragalla HE, Aly SM. Association of Cytokeratin and Vimentin Protein in the Genesis of Transitional Cell Carcinoma of Urinary Bladder Patients. Disease Markers.
  15. 2015; 2015: 204759. https://www.ncbi.nlm.nih.gov/pubmed/26640315. https://www.ncbi.nlm.nih.gov/pmc/articles/4660019. https://doi.org/10.1155/2015/204759
  16. Sayan AE, Griffiths TR, Pal R, Browne GJ, Ruddick A, Yagci T, et al. SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106(35): 14884–9. https://www.ncbi.nlm.nih.gov/pubmed/19706487. https://www.ncbi.nlm.nih.gov/pmc/articles/2736415. https://doi.org/10.1073/pnas.0902042106
  17. Slaton JW, Millikan R, Inoue K, Karashima T, Czerniak B, Shen Y, et al. Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy. Journal of Urology. 2004; 171(2 Pt 1): 570–4. https://www.ncbi.nlm.nih.gov/pubmed/14713761. https://doi.org/10.1097/01.ju.0000108845.91485.20
  18. Sledge DG, Patrick DJ, Fitzgerald SD, Xie Y, Kiupel M. Differences in Expression of Uroplakin III, Cytokeratin 7, and Cyclooxygenase-2 in Canine Proliferative Urothelial Lesions of the Urinary Bladder. Veterinary Pathology. 2015; 52(1): 74–82. https://www.ncbi.nlm.nih.gov/pubmed/24608632. https://doi.org/10.1177/0300985814522819
  19. Yalçin Ö, Sağlican Y, Özdemir S, Özkan N, Mangir N, Eren F. The Relationship of p16, Ki-67, Bcl-2, P53 and CK20 Immune Expressions with Recurrence in Superficial Bladder Tumors. World Journal of Pathology. 2015; 8: 44–51.