Correlation of Muscle Invasion in Bladder Cancer with Cell Adhesion Properties and Oncoprotein Overexpression Using E-Cadherin and HER2/neu Immunohistochemical Markers.
DOI:
https://doi.org/10.3889/oamjms.2020.3388Keywords:
Bladder cancers, Non-muscle invasive bladder cancer, Muscle invasive bladder cancer, E-cadherin, Human epidermal growth factor receptor-2Abstract
BACKGROUND: Most of bladder cancers are proven to be of urothelial origin (transitional cell carcinomas). Above 75% of them are of non-muscle invasive bladder cancer (NMIBC) type at presentation and the remainder are MIBC. Recent studies suggest that both are most probably two different categories based on both the histopathological and molecular features. The comprehensive understanding of the biomarkers expression in both categories will help in understanding the molecular event underlying each of them and may provide possible chances for targeted therapeutic options.
AIM: This study aims to study the differential expression of both E-cadherin and human epidermal growth factor receptor-2 (HER2) in the two categories of bladder cancer NMIBCs and MIBCs.
MATERIALS AND METHODS: A total of 40 blocks were collected retrospectively from cases of cancer bladder, segregated as 20 cases NMIBCs and 20 cases MIBCs, subjected for E-cadherin and HER2 immunostaining.
RESULTS: E-cadherin showed positive expression in 65% of cases of NMI group and in 10% of the MI group, with high statistical significance (p < 0.001). Regarding HER2, positive expression was seen in 25% of NMI cases and in 90% of MI cases, with statistical significance (p < 0.001). Comparison of the results of both markers and their correlation per case showed that 90% of tumors with muscle invasion were E-cadherin negative and HER2 positive.
CONCLUSION: The significant association of loss of E-cadherin immunohistochemistry expression and positive HER2 overexpression in MIBC versus NMIBC figured out more differences between the two categories and added to the understanding of their biology. The possibility of validation of HER2-targeted therapy in MIBC cases is now strongly suggested.
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Marcelino Y, Peter W, Sunjay J. Bladder cancer. Medicine. 2016;44(1):52-5.
Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009;27(3):289-93. https://doi.org/10.1007/s00345-009-0383-3 PMid:19219610
Zheng YL, Amr S, Saleh D, Dash C, Ezzat S, Mikhail NN, et al. Urinary bladder cancer risk factors in Egypt response. Cancer Epidemiol Biomarkers Prev. 2012;21(3):537-46. https://doi. org/10.1158/1055-9965.epi-11-0589
Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374(9685):239-49. https://doi.org/10.1016/ s0140-6736(09)60491-8
Sanguedolce F, Cormio A, Calт B, Buffi N, Autorino R, Cormi L. Molecular markers predicting disease outcome in bladder cancer. Should we shift from the classical cell-cycle regulators to HER2 oncogene? GGJ. 2018;66:239-44.
Sjцdahl G, Jackson CL, Bartlett JM, Siemens DR, Berman DM. Molecular profiling in muscle-invasive bladder cancer: More than the sum of its parts. J Pathol. 2019;247:563-73. https://doi. org/10.1002/path.5230
PMid:30604486
Mohammed AA, El-Tanni H, El-Khatib HM, Mirza AA, Mirza AA, Alturaifi TH. Urinary bladder cancer: Biomarkers and target therapy, new era for more attention. Oncol Rev. 2016;10(2):320. https://doi.org/10.4081/oncol.2016.320
Singh A, Settleman J. EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741-51. https://doi.org/10.1038/ onc.2010.215 PMid:20531305
Bryan RT, Atherfold PA, Yeo Y, Jones LJ, Harrison RF, Wallace DM, et al. Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: Ex vivo and in vitro studies. J Pathol. 2008;215(2):184-94. https://doi.org/10.1002/ path.2346 PMid:18393367
Petrova YI, Schecterson L, Gumbiner BM. Roles for E cadherin cell surface regulation in cancer. Mol Biol Cell. 2016;27(21):3181- 375. https://doi.org/10.1091/mbc.e16-01-0058
Zhao J, Xu W, Zhang Z, Song R, Zeng S, Xu C. Prognostic role of HER2 expression in bladder cancer: a systematic review and meta analysis. Int Urol Nephrol. 2015;47(1):87-94. https://doi. org/10.1007/s11255-014-0866-z
PMid:25384433
Powles, T., Huddart R. Elliot T. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor1/2 positive metastaic bladder cancer. J Clin Oncol. 2016;66:3468. https://doi.org/10.1016/j. eururo.2017.05.027
Kiss B, Wyatt AW, Douglas J, Skuginna V, Mo F, Anderson S, et al. HER2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy. Sci Rep. 2017;16(7):42713. https://doi.org/10.1038/ srep42713
Ai M, Liang K, Lu Y, Qiu S, Fan Z. Brk/PTK6 cooperates with HER2 and Src in regulating breast cancer cell survival and epithelial-to-mesenchymal transition. Cancer Biol Ther. 2013;14(3):237-45. https://doi.org/10.4161/cbt.23295 PMid:23291984
Wang M, Ren D, Guo W, Huang S, Wang Z, Li Q, et al. N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells. Int J Oncol. 2015;48(2):595-606. https://doi.org/10.3892/ ijo.2015.3270 PMid:26647992
Carneiro BA, Meeks JJ, Kuzel TM, Scaranti M, Abdulkadir SA, Giles FJ. Emerging therapeutic targets in bladder cancer. Cancer Treatment Rev. 2015;41(2):170-8. https://doi.org/10.1016/j. ctrv.2014.11.003 PMid:25498841
Morera DS, Hennig MS, Talukder A, Lokeshwar SD, Wang J, Garcia-Roig M, et al. Hyaluronic acid family in bladder cancer: Potential prognostic biomarkers and therapeutic targets. Br J Cancer. 2017;117(10):1507-17. https://doi.org/10.1038/ bjc.2017.318 PMid:28972965
Otto W, Breyer J, Herdegen S, Eder F, Bertz S, May M, et al. WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach. Int Urol Nephrol. 2017;49(3):431- 7. https://doi.org/10.1007/s11255-016-1491-9 PMid:28035618
Kolla SB, Seth A, Singh MK, Gupta NP, Hemal AK, Dogra PN, et al. Prognostic significance of HER2/neu overexpression in patients with muscle invasive urinary bladder cancer treated with radical cystectomy. Int Urol Nephrol. 2008;40(2):321-7. https://doi.org/10.1007/s11255-007-9283-x PMid:17899426
Kyritsi F, Loffredo CA, Zheng YL, Philips G, Amr S. Urinary bladder cancer in Egypt: Are there gender differences in its histopathological presentation? Adv Urol. 2018;13:3453808. https://doi.org/10.1155/2018/3453808
Jдger T, Becker M, Eisenhardt A, Tilki D, Tцtsch M, Schmid KW, et al. The prognostic value of cadherin switch in bladder cancer. Oncol Rep. 2010;23(4):1125-32. PMid:20204300
Baumgart E, Cohen MS, Neto BS, Jacobs MA, Wotkowicz C, Rieger-Christ KM, et al. Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res. 2007;13(6):1685-94. https://doi.org/10.1158/1078-0432.ccr-06-2330 PMid:17363521
D’Andrea D, Hassler MR, Abufaraj M, Soria F, Ertl IE, Ilijazi D, et al. Progressive tissue biomarker profiling in non-muscle-invasive bladder cancer. Expert Rev Anticancer Ther. 2018;18(7):695-703. https://doi.org/10.1080/14737140.2018.14 74104 PMid:29737231
Kashibuchi K, Tomita K, Schalken JA, Kume H, Takeuchi T, Kitamura T. The prognostic value of E-cadherin, alpha-, beta- and gamma-catenin in bladder cancer patients who underwent radical cystectomy. Int J Urol. 2007;14(9):789-94. https://doi.org/10.1111/j.1442-2042.2007.01830.x PMid:17760743
Hu X, Ruan Y, Cheng F, Yu W, Zhang X, Larré S. p130Cas, E-cadherin and β-catenin in human transitional cell carcinoma of the bladder: Expression and clinicopathological significance. Int J Urol. 2011;18(9):630-7. https://doi. org/10.1111/j.1442-2042.2011.02793.x PMid:21672035
Hammam O, Nour HH, Mosaad M, Akl M, Khalil H, Al Ganzory H, et al. The clinical significance of HER2 protein amplification/expression in urinary bladder lesion. Arab J Urol. 2015;13(2):146-52. https://doi.org/10.1016/j.aju.2015.01.004 PMid:26413337
Tschui J, Vassella E, Bandi N, Baumgartner U, Genitsch V, Rotzer D, et al. Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer. Virchows Archiv Heidelberg. 2015;466(6):703-10. https://doi.org/10.1007/ s00428-015-1729-4 PMid:25809292
Latif Z, Watters AD, Dunn I, Grigor KM, Underwood MA, Bartlett JM. HER2/neu overexpression in the development of muscle- invasive transitional cell carcinoma of the bladder. Br J Cancer. 2003; 89(7):1305-9. https://doi.org/10.1038/ sj.bjc.6601245 PMid:14520464
Agrawal V, Mandhani A, Pandey R, Agarwal V. HER2/neu 2+ protein expression by immunohistochemistry in urothelial bladder cancer is not associated with gene amplification by in situ hybridization. Am J Clin Pathol. 2015;144(2):A376. https:// doi.org/10.1093/ajcp/144.suppl2.376
Ding W, Tong S, Gou Y, Sun C, Wang H, Chen Z, et al. Human epidermal growth factor receptor 2: A significant indicator for predicting progression in non-muscle-invasive bladder cancer especially in high- risk groups. World J Urol. 2015;33(12):1951- 7. https://doi.org/10.1007/s00345-015-1557-9
Vidal RM, Mota SR, Hayden A, Markham H, Douglas J, Packham G, et al. Epidermal growth factor receptor family inhibition identifies p38 mitogen-activated protein kinase as a potential therapeutic target in bladder cancer. Urology. 2018;112(225):e1-225.e7. https://doi.org/10.1016/j. urology.2017.10.041 PMid:29154981
Nagata M, Muto S, Horie S. Molecular biomarkers in bladder cancer: Novel potential indicators of prognosis and treatment outcomes. Dis Markers. 2016;2016:8205836. https://doi. org/10.1155/2016/8205836 PMid:26924873
Breyer J, Otto W, Wirtz RM, Wullich B, Keck B, Erben P, et al. ERBB2 expression as potential risk-stratification for early cystectomy in patients with pT1 bladder cancer and concomitant carcinoma in situ. Urol Int. 2017;98(3):282-9. https://doi. org/10.1159/000453670 PMid:27992871
Sanguedolce F, Russo D, Mancini V, Selvaggio O, Calт B, Pagliarulo V, et al. Human epidermal growth factor receptor 2 in non-muscle invasive bladder cancer: Issues in assessment methods and its role as prognostic/predictive marker and putative therapeutic target: A comprehensive review. Urol Int. 2018;21:1-13. https://doi.org/10.1159/000494359
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Copyright (c) 2020 Reham Shehab El Nemr Esmail, Lubna Omer Abdel-Salam , Mohamed Mahmoud Abdellah (Author)
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