Document Type : Original Research

Authors

1 Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Research and Development Center Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

10.30699/ijp.2020.130859.2447

Abstract

Background and Objective: Urothelial neoplasm (UN) of bladder is a potentially lethal malignancy, particularly in locally advanced or metastatic cases. Development of molecular markers such as HER2 and Survivin may provide useful information on diagnosis and prognosis in UN of bladder.
Materials and Methods: We studied the immunohistochemical (IHC) expression of HER2 and Survivin in 84 radical/partial cystectomy and transurethral resection (TUR) specimens with different histologic grades and stages.  All samples were obtained from pathology department of Sina Hospital in Tehran, Iran from 2014 to 2018.
Results: From the total number of 84 UN samples, 10 cases (11.9%) had papillary neoplasm of low malignant potential, 30 cases (35.7%) had low-grade papillary urothelial neoplasm, and 44 cases (52.4%) had high-grade papillary urothelial neoplasm. HER2 and Survivin expressions were seen in 44 (52.4%) (p =0.610) and 9 (10.7%) patients (p =0.046), respectively.Survivin expression showed a mild increase in high grade UN.
Conclusion: Our findings suggest that the IHC expression of Survivin and HER2 are not well associated with histological grades of Urothelial neoplasms of bladder. This may be partly due to relatively small sample size and various factors such as patient characteristics or antibody specifications.

Highlights

  • Urothelial neoplasm (UN) is one of the most common cancers.
  • Survivin and HER2 may be related with histological grade of UN.
  • Survivin expression showed a mild increase in high grade UN.

Keywords

Main Subjects

Nedjadi T, Al-Maghrabi J, Assidi M, Dallol A, Al-Kattabi H, Chaudhary A, et al. Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques. BMC Cancer. 2016;16:653. [DOI:10.1186/s12885-016-2703-5] [PMID] [PMCID]

Cumberbatch MGK, Noon AP. Epidemiology, aetiology and screening of bladder cancer. Transl Androl Urol. 2019;8(1):5-11. [DOI:10.21037/tau.2018.09.11] [PMID] [PMCID]

Sharp JD, Hausladen DA, Maher MG, Wheeler MA, Altieri DC, Weiss RM. Bladder cancer detection with urinary survivin, an inhibitor of apoptosis. Front Biosci. 2002;7(1):e36-41. [DOI:10.2741/sharp] [PMID]

Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2005;66(6 Suppl 1):4-34. [DOI:10.1016/j.urology.2005.07.062] [PMID]

Tolkach Y, Stahl AF, Niehoff EM, Zhao C, Kristiansen G, Muller SC, et al. YRNA expression predicts survival in bladder cancer patients. BMC Cancer. 2017;17(1):749. [DOI:10.1186/s12885-017-3746-y] [PMID] [PMCID]

Tan WS, Tan WP, Tan MY, Khetrapal P, Dong L, deWinter P, et al. Novel urinary biomarkers for the detection of bladder cancer: A systematic review. Cancer Treat Rev. 2018;69:39-52. [DOI:10.1016/j.ctrv.2018.05.012] [PMID]

Koletsas N, Koletsa T, Choidas S, Anagnostopoulos K, Touloupidis S, Zaramboukas T, et al. Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas. Patholog Res Int. 2017;2017:6794150. [DOI:10.1155/2017/6794150] [PMID] [PMCID]

Chou R, Gore JL, Buckley D, Fu R, Gustafson K, Griffin JC, et al. Urinary Biomarkers for Diagnosis of Bladder Cancer: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163(12):922-31. [DOI:10.7326/M15-0997] [PMID]

Jin H, Lin T, Han P, Yao Y, Zheng D, Hao J, et al. Efficacy of Raman spectroscopy in the diagnosis of bladder cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(47):e18066. [DOI:10.1097/MD.0000000000018066] [PMID] [PMCID]

Liang Z, Xin R, Yu Y, Wang R, Wang C, Liu X. Diagnostic value of urinary survivin as a biomarker for bladder cancer: a systematic review and meta-analysis of published studies. World J Urol. 2018;36(9):1373-81. [DOI:10.1007/s00345-018-2285-8] [PMID]

El-Hakim TFA, El-Shafie MK, Abdou AG, Azmy RM, El-Naidany SS, El-Din MOB. Value of urinary survivin as a diagnostic marker in bladder cancer. Anal Quant Cytopathol Histpathol. 2014;36(3):121-7.

Weikert S, Christoph F, Schrader M, Krause H, Miller K, Muller M. Quantitative analysis of survivin mRNA expression in urine and tumor tissue of bladder cancer patients and its potential relevance for disease detection and prognosis. Int J Cancer. 2005;116(1):100-4. [DOI:10.1002/ijc.21000] [PMID]

Ohsawa I, Nishimura T, Kondo Y, Kimura G, Satoh M, Matsuzawa I, et al. Detection of urine survivin in 40 patients with bladder cancer. J Nippon Med Sch. 2004;71(6):379-83. [DOI:10.1272/jnms.71.379] [PMID]

Margulis V, Lotan Y, Shariat SF. Survivin: a promising biomarker for detection and prognosis of bladder cancer. World J Urol. 2008;26(1):59-65. [DOI:10.1007/s00345-007-0219-y] [PMID]

Smith SD, Wheeler MA, Plescia J, Colberg JW, Weiss RM, Altieri DC. Urine detection of survivin and diagnosis of bladder cancer. JAMA. 2001;285(3):324-8. [DOI:10.1001/jama.285.3.324] [PMID]

Memon AA, Sorensen B, Meldgaard P, Fokdal L, Thykjaer T, Nexo E. The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4: a study in bladder cancer patients. Br J Cancer. 2006;94(11):1703-9. [DOI:10.1038/sj.bjc.6603154] [PMID] [PMCID]

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 Arch. 2015;466(6):703-10. [DOI:10.1007/s00428-015-1729-4] [PMID] [PMCID]

Abdelrahman AE, Rashed HE, Elkady E, Elsebai EA, El-Azony A, Matar I. Fatty acid synthase, Her2/neu, and E2F1 as prognostic markers of progression in non-muscle invasive bladder cancer. Ann Diagn Pathol. 2019;39:42-52. [DOI:10.1016/j.anndiagpath.2019.01.002] [PMID]

Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol. 2016;70(1):106-19. [DOI:10.1016/j.eururo.2016.02.028] [PMID]

Fitzgibbons PL, Lazar AJ, Spencer S. Introducing new College of American Pathologists reporting templates for cancer biomarkers. Arch Pathol Lab Med. 2014;138(2):157-8. [DOI:10.5858/arpa.2013-0233-ED] [PMID]

Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(1):18-43. [DOI:10.1200/JCO.2006.09.2775]

Breyer J, Gierth M, Shalekenov S, Aziz A, Schäfer J, Burger M, et al. Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma. World J Urol. 2016;34(5):709-16. [DOI:10.1007/s00345-015-1690-5] [PMID]

Xi RC, Sheng YR, Chen WH, Sheng L, Gang JJ, Tong Z, et al. Expression of survivin and livin predicts early recurrence in non-muscle invasive bladder cancer. J Surg Oncol. 2013;107(5):550-4. [DOI:10.1002/jso.23272] [PMID]

Zhao J, Xu W, Zhang Z, Song R, Zeng S, Sun Y, et al. Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis. Int Urol Nephrol. 2015;47(1):87-94. [DOI:10.1007/s11255-014-0866-z] [PMID]

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. [DOI:10.1007/s11255-007-9283-x] [PMID]

Schultz I, Kiemeney L, Witjes J, Schalken J, Willems J, Swinkels D, et al. Survivin mRNA expression is elevated in malignant urothelial cell carcinomas and predicts time to recurrence. Anticancer Res. 2003;23(4):3327-32.

Salz W, Eisenberg D, Plescia J, Garlick DS, Weiss RM, Wu XR, et al. A survivin gene signature predicts aggressive tumor behavior. Cancer Res. 2005;65(9):3531-4. [DOI:10.1158/0008-5472.CAN-04-4284] [PMID]

Akhtar M, Gallagher L, Rohan S. Survivin: role in diagnosis, prognosis, and treatment of bladder cancer. Adv Anat Pathol. 2006;13(3):122-6. [DOI:10.1097/00125480-200605000-00003] [PMID]

Shariat SF, Ashfaq R, Karakiewicz PI, Saeedi O, Sagalowsky AI, Lotan Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2007;109(6):1106-13. [DOI:10.1002/cncr.22521] [PMID]

Als AB, Dyrskjot L, von der Maase H, Koed K, Mansilla F, Toldbod HE, et al. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res. 2007;13(15 Pt 1):4407-14. [DOI:10.1158/1078-0432.CCR-07-0109] [PMID]

Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol. 2011;60(2):350-7. [DOI:10.1016/j.eururo.2011.05.035] [PMID]

Eltze E, Wulfing C, Von Struensee D, Piechota H, Buerger H, Hertle L. Cox-2 and Her2/neu co-expression in invasive bladder cancer. Int J Oncol. 2005;26(6):1525-31. [DOI:10.3892/ijo.26.6.1525] [PMID]

Ning S, Fuessel S, Kotzsch M, Kraemer K, Kappler M, Schmidt U, et al. siRNA-mediated down-regulation of survivin inhibits bladder cancer cell growth. Int J Oncol. 2004;25(4):1065-71. [DOI:10.1016/S1569-9056(04)90204-7]

Lehner R, Lucia MS, Jarboe EA, Orlicky D, Shroyer AL, McGregor JA, et al. Immunohistochemical localization of the IAP protein survivin in bladder mucosa and transitional cell carcinoma. Appl Immunohistochem Mol Morphol. 2002;10(2):134-8. [DOI:10.1097/00129039-200206000-00007] [PMID]