A Immunohistochemical expression of Bcl-2 and EGFR biomarkers in Urothelial carcinoma of the bladder lesions and its relation to grade

Immunohistochemical expression of Bcl-2 and EGFR biomarkers in Urothelial carcinoma


  • Naghmeh Mostafaee
  • Elnaz Sheikhpour
  • mahmood Akhavan
  • Azam Hashemi
  • Fatemeh Daneshmand


Bcl-2, biomarkers, epidermal growth factor receptor, urothelial carcinoma




Over-expression of Bcl-2 and EGFR is seen in many malignancies. Since few studies have studied these biomarkers in bladder tumors, the aim of this study is to evaluate expression of Bcl-2 and EGFR biomarkers in benign and malignant tumors of urothelial carcinoma of bladder.


This case control study was conducted on 57 bladder tumors (40 malignant tumors and 17 benign tumors) in Shahid Rahnemoun hospital, Yazd, Iran during 2016-2018. Immunohistochemistry method was used for assessment of EGFR and bcl-2 expression in tissue tumors.


Frequency distribution of patients in terms of EGFR showed that among 57 tumors, 10 tumors (17.4%) were EGFR positive. Moreover, among them, 25 tumors were bcl-2 positive (44%). There was no significant difference between benign and malignant tumors in terms of EGFR (p=0.830) and bcl-2 expression (p=0.094). The mean EGFR in low and high grade was 4.13± 13.22 and 7.69± 26.26, respectively (p= 0.91).The mean bcl-2 in low and high grade was 3.72± 12.81 and 13.31±26.14, respectively (p=0.51). Moreover, significant difference was seen between two groups (benign and malignant group), regarding age and tumor size (p>0.05).



According to results of current study, no significant difference was seen between benign and malignant tumors in terms of EGFR and bcl-2 expression. Moreover, no relation was seen between EGFR and Bcl2 expression and grade. Therefore, expression of these biomarkers didn't affect on progression of the tumor and clinical outcomes. In addition, malignant or benign tumor was affected by factors including age and tumor size.


1.Rafiemanesh H, Lotfi Z, Bakhtazad S, Ghoncheh M, Salehiniya H. The epidemiological and histological trend of bladder cancer in Iran. J Cancer Res Ther. 2018;14(3):532-536.
2. Carlsson J, Wester K, De La Torre M, Malmstr.m PU, Gardmark T. EGFRexpressionin primary urinary bladder cancer and corresponding metastasesand the relation to HER2- expression. On the possibility to target thesereceptors with radionuclides. RadiolOncol. 2015
Mar 3;49(1):50–8.
3. Landis SH, Murrav T, Boldeni S, W'ingo PA. Cancer statistics, 1999. CA Cancer J Clin. 1999;49:8-31
4. Ye YK, Bi XC, He HC, Han ZD, Dai QS, Liang YX, Zeng GH, Qin WJ, Chen ZN, Zhong WD. CK20 and Ki-67 as significant prognostic factors in human bladder carcinoma. Clin Exp Med. 2010 Sep;10(3):153-8
5.Neal D Freedman, Debra T Silverman, Albert R Hollenbeck, Arthur Schatzkin, Christian C Abnet. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011 Aug 17; 306(7): 737–745.
6.D'Avanzo B, Negri E, La Vecchia C, Gramenzi A, Bianchi C, Franceschi S, Boyle P. Cigarette smoking and bladder cancer. Eur J Cancer. 1990;26(6):714-8.
7.Neal D. Freedman, Debra T. Silverman, ScD, ScM; Albert R. Hollenbeck. Association Between Smoking and Risk of Bladder Cancer Among Men and Women. JAMA. 2011;306(7):737-745
8. Tobacco Smoke and Involuntary Smoking. In: IARC Monographs on the Evaluation of Carcinogenic Risk to Humans. Vol 83. Lyon, France: IARC; 2004.
9. Chung K. The Etiology of Bladder Cancer and its Prevention. J Cancer Sci Ther 2013; 5(10): 346-361

10.Taleb S. C-kit and Bcl2 in bladder carcinoma:An immunohistochemical study. AAMJ 2013; 11(1): 214-227.
11.Hashmi A, Fida Hussain Z, Muhammad Irfan, Erum Yousuf Khan, Naveen Faridi, Hanna Naqvi, Amir Khan, Muhammad Muzzammil Edhi. BMC Urology 2018; 18:59

12. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2: 127-37.
13.Cook W, R. Ganesan, A. Burton ,L.S. Young , CookeN.D. James. Bcl‐2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy. BJUI 2001
14.Swellam M1, Abd-Elmaksoud N, Halim MH, Khatab H, Khiry H. Incidence of Bcl-2 expression in bladder cancer: relation to schistosomiasis. Clin Biochem. 2004 Sep;37(9):798-802

15.Glick SH, Howel LP, White WD. Relationship of p53 and bcl-2 to prognosis in muscle
invasive TCC of the bladder. J Urol 1996; 155:1754– 7.
16.Kadkhodayan S. Evaluation of the frequency of BCL2 and P53 and angiogenesis in endometrial cancer and its relationship with clinicopathological characteristics. IJOGI 2015; 18:1-7.

17.Railka R, L, Krane S, Q. Quentin Li, Thomas Sanford1, Mohammad Rashid Siddiqui1, Diana Haines, Srinivas Vourganti1 , Sam J. Brancato1, Peter L. Choyke, Hisataka Kobayashi, Piyush K. Agarwa. Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder. Mol Cancer Ther. 2017 ; 16(10): 2201–2214

18. Enache N M, Eugenia S C. EGFR and Her2/neuimmunoexpression in papillary urothelial
bladder carcinomas. Romanian Journal MorphologyEmbryology.2013, 54:137–141.

19..Lopez-Beltran A, Sauter G, Gasser T, Tumours of the urinary system. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds), Pathology and genetics of tumours of the urinary system and male genital organs, World Health Organization Classification of Tumours, IARC Press, Lyon, 2004; 89– 154.
20 Rotterud R, Nesland JM, Berner A, Fossa SD. Expression of the epidermal growth factor receptor family in normal and malignant urothelium. BJU international. 2005; 95(9):1344–50.

21.Rebouissou S, Bernard-Pierrot I, de Reynies A, Lepage ML, Krucker C, Chapeaublanc E, et al. EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Science translational medicine. 2014; 6(244):244ra91.

22. korkolopoulou P , Andreas ch.Lazaris;Anastasia – E. Konostantinidou , Nikolaoskavantzas and et al. Differential expression of bcl2 family proteins in bladder carcinomas relationship with apaptotic rate and survival rate; European urology; 2002 ;p:274
– 283

23.Cho HJ, Kim JK, Kim KD, Yoon HK, Cho MY, Park YP, Jeon JH, LeeES, Byun SS, Lim HM: Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation inhuman bladder cancer cells. Cancer Lett 2006, 237:56-66.

24. White, ScD, Dawn M. Holman, MPH, Jennifer E. Boehm, MPH, Lucy A. Peipins Age and Cancer Risk:Am J Prev Med. 2014 March ; 46(3 0 1): S7–15

25.Thompson RH, Kurta JM, Kaag M, Tickoo SK, Kundu S, Katz D, Nogueira L, Reuter VE, Russo P.Tumor size is associated with malignant potential in renal cell carcinoma cases. J Urol. 2009 May;181(5):2033-6.

26.Cheng LCheng L. Neumann RM, Scherer BG, Weaver AL, Leibovich BC, Nehra A, Zincke H, Bostwick DG.Tumor size predicts the survival of patients with pathologic stage T2 bladder carcinoma: a critical evaluation of the depth of muscle invasion.Cancer. 1999 Jun 15;85(12):2638-47

27.Brandt J, Garne J, Tengrup I, Manjer J.Age at diagnosis in relation to survival following breast cancer: a cohort study.World Journal of Surgical Oncology 2015;13:1-9.






Original Article