CLINICAL IMMUNOLOGY
Expression of E-cadherin, β-catenin, and epithelial membrane antigen does not predict survival in patients with high-risk non-muscle-invasive bladder cancer
Submission date: 2018-01-14
Final revision date: 2018-03-16
Acceptance date: 2018-04-23
Publication date: 2018-12-31
Cent Eur J Immunol 2018;43(4):421-427
KEYWORDS
ABSTRACT
The aim of the study:
was to validate the value of E-cadherin and β-catenin expression and to test an alternative prognostic marker, epithelial membrane antigen (EMA).
Material and methods:
Forty-nine consecutive patients with primary stage T1 non-muscle-invasive bladder cancer (NMIBC) were enrolled in this study. Tissue specimens were stained with the following mouse anti-human antibodies: anti-E-cadherin, anti-β-catenin, and anti-EMA. Reaction intensity within cancer cells was assessed according to the immunoreactive score (IRS). Finally, the association between the expression of selected proteins and patient survival was assessed.
Results:
The mean follow-up was 34.8 months. Recurrence-free survival, progression-free survival, and overall survival (OS) were 47.5%, 72.5%, and 72.5%, respectively. Differences in the IRS for β-catenin and EMA were found clinically, but were not statistically significant in prediction of the risk of disease progression (p > 0.05). No difference in protein expression was observed regarding the risk of recurrence, OS, or cancer-specific mortality (p > 0.05). Stratification of patients based on the IRS into three groups (poor, moderate, and intensive reaction) failed to identify a prognostic marker among the tested proteins (p > 0.05).
Conclusions:
Expression of E-cadherin, β-catenin, and EMA cannot reliably predict survival in patients with high-risk NMIBC. Further searches are needed to identify tissue markers of progression and recurrence in NMIBC.
was to validate the value of E-cadherin and β-catenin expression and to test an alternative prognostic marker, epithelial membrane antigen (EMA).
Material and methods:
Forty-nine consecutive patients with primary stage T1 non-muscle-invasive bladder cancer (NMIBC) were enrolled in this study. Tissue specimens were stained with the following mouse anti-human antibodies: anti-E-cadherin, anti-β-catenin, and anti-EMA. Reaction intensity within cancer cells was assessed according to the immunoreactive score (IRS). Finally, the association between the expression of selected proteins and patient survival was assessed.
Results:
The mean follow-up was 34.8 months. Recurrence-free survival, progression-free survival, and overall survival (OS) were 47.5%, 72.5%, and 72.5%, respectively. Differences in the IRS for β-catenin and EMA were found clinically, but were not statistically significant in prediction of the risk of disease progression (p > 0.05). No difference in protein expression was observed regarding the risk of recurrence, OS, or cancer-specific mortality (p > 0.05). Stratification of patients based on the IRS into three groups (poor, moderate, and intensive reaction) failed to identify a prognostic marker among the tested proteins (p > 0.05).
Conclusions:
Expression of E-cadherin, β-catenin, and EMA cannot reliably predict survival in patients with high-risk NMIBC. Further searches are needed to identify tissue markers of progression and recurrence in NMIBC.
REFERENCES (33)
1.
van den Bosch S, Witjes JA (2011): Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review. Eur Urol 60: 493-500.
2.
Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. (2006): Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49: 466-75.
3.
Fernandez-Gomez J, Madero R, Solsona E, et al. (2009): Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J Urol 182: 2195-203.
4.
Ali-El-Dein B, Al-Marhoon MS, Abdel-Latif M, et al. (2011): Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder. Urol Ann 3: 127-132.
5.
Hautmann RE, Volkmer BG, Gust K (2009): Quantification of the survival benefit of early versus deferred cystectomy in high-risk non-muscle invasive bladder cancer (T1 G3). World J Urol 27: 347-351.
6.
May M, Bastian PJ, Brookman-May S, et al. (2011): Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder. Scand J Urol Nephrol 45: 251-257.
7.
Cheng L, Davison DD, Adams J, et al. (2014): Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hematol 89: 73-111.
8.
Sun W, Herrera GA (2002): E-cadherin expression in urothelial carcinoma in situ, superficial papillary transitional cell carcinoma, and invasive transitional cell carcinoma. Hum Pathol 33: 996-1000.
9.
Lee JM, Dedhar S, Kalluri R, Thompson EW (2006): The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 172: 973-981.
10.
Erdemir F, Ozcan F, Kilicaslan I, et al. (2007): The relationship between the expression of E-cadherin and tumor recurrence and progression in high-grade stage T1 bladder urothelial carcinoma. Int Urol Nephrol 39: 1031-1037.
11.
Khorrami MH, Hadi M, Gharaati MR, et al. (2012): E-cadherin expression as a prognostic factor in transitional cell carcinoma of the bladder after transurethral resection. Urol J 9: 581-585.
12.
Muramaki M, Miyake H, Terakawa T, et al. (2012): Expression profile of E-cadherin and N-cadherin in non-muscle-invasive bladder cancer as a novel predictor of intravesical recurrence following transurethral resection. Urol Oncol 30: 161-166.
13.
Liu B, Miyake H, Nishikawa M, et al. (2015): Expression profile of epithelial-mesenchymal transition markers in non-muscle-invasive urothelial carcinoma of the bladder: correlation with intravesical recurrence following transurethral resection. Urol Oncol 33: 110 e11-8.
14.
Mahnken A, Kausch I, Feller AC, et al. (2005): E-cadherin immunoreactivity correlates with recurrence and progression of minimally invasive transitional cell carcinomas of the urinary bladder. Oncol Rep 14: 1065-1070.
15.
Raspollini MR, Luque RJ, Menendez CL, et al. (2016): T1 High Grade Bladder Carcinoma Outcome: The Role of P16, Topoisomerase-Ii Alpha, Survivin and E-Cadherin. Hum Pathol 57: 78-84.
16.
Zhao J, Dong D, Sun L, et al. (2014): Prognostic significance of the epithelial-to-mesenchymal transition markers e-cadherin, vimentin and twist in bladder cancer. Int Braz J Urol 40: 179-189.
17.
Breyer J, Gierth M, Shalekenov S, et al. (2016): Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma. World J Urol 34: 709-716.
18.
Thoreson MA, Reynolds AB (2002): Altered expression of the catenin p120 in human cancer: implications for tumor progression. Differentiation 70: 583-589.
19.
Hu X, Ruan Y, Cheng F, et al. (2011): p130Cas, E-cadherin and beta-catenin in human transitional cell carcinoma of the bladder: expression and clinicopathological significance. Int J Urol 18: 630-637.
20.
Shimazui T, Schalken JA, Giroldi LA, et al. (1996): Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. Cancer Res 56: 4154-4158.
21.
Schrier BP, Vriesema JL, Witjes JA, et al. (2006): The predictive value of p53, p27(kip1), and alpha-catenin for progression in superficial bladder carcinoma. Eur Urol 50: 76-82.
22.
Senol S, Yildirim A, Ceyran B, et al. (2015): Prognostic significance of survivin, beta-catenin and p53 expression in urothelial carcinoma. Bosn J Basic Med Sci 15: 7-14.
23.
Clairotte A, Lascombe I, Fauconnet S, et al. (2006): Expression of E-cadherin and alpha-, beta-, gamma-catenins in patients with bladder cancer: identification of gamma-catenin as a new prognostic marker of neoplastic progression in T1 superficial urothelial tumors. Am J Clin Pathol 125: 119-126.
24.
Kashibuchi K, Tomita K, Schalken JA, et al. (2006): The prognostic value of E-cadherin, alpha-, beta-, and gamma-catenin in urothelial cancer of the upper urinary tract. Eur Urol 49: 839-845.
25.
Reis ST, Leite KR, Mosconi Neto A, et al. (2012): Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas. Int Braz J Urol 38: 466-473.
26.
Lin W, Liu X, Cen Y (2016): Diagnostic accuracy of epithelial membrane antigen for malignant effusions: a meta-analysis. Int J Biol Markers 31: e11-16.
27.
Takashi M, Murase T, Kinjo T, et al. (1987): Epithelial membrane antigen as an immunohistochemical marker for transitional cell carcinoma of the urinary bladder. Urol Int 42: 170-175.
28.
Asamoto M, Fukushima S, Oosumi H, et al. (1989): Immunohistochemical distribution of epithelial membrane antigen in bladder carcinomas as detected with a monoclonal antibody. Urol Res 17: 273-277. Ring KS, Karp F, Benson MC (1990): Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report. J Occup Med 32: 904-909.
29.
Tanaka K, Takashi M, Miyake K, et al. (1994): Immunocytochemically demonstrated expression of epithelial membrane antigen and carcinoembryonic antigen by exfoliated urinary cells in patients with bladder cancer. Urol Int 52: 140-144.
30.
Attallah AM, El-Far M, Abdallah SO, et al. (2015): Combined use of epithelial membrane antigen and nuclear matrix protein 52 as sensitive biomarkers for detection of bladder cancer. Int J Biol Markers 30: e407-413.
31.
Lambert EH, Pierorazio PM, Olsson CA, et al. (2007): The increasing use of intravesical therapies for stage T1 bladder cancer coincides with decreasing survival after cystectomy. BJU Int 100: 33-36.
32.
Margel D, Tal R, Golan S, et al. (2007): Long-term follow-up of patients with Stage T1 high-grade transitional cell carcinoma managed by Bacille Calmette-Guerin immunotherapy. Urology 69: 78-82.
33.
Pansadoro V, Emiliozzi P, de Paula F, et al. (2002): Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guerin: 18-year experience. Urology 59: 227-231.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
