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Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis

  • Urology – Review
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Abstract

Objective

The prognostic role of human epidermal growth factor receptor 2 (HER2) in bladder cancer (BCa) remains controversial. Thus, we conducted a meta-analysis to assess the prognostic significance of HER2 for patients with BCa.

Materials and methods

Systematically computerised searching in PubMed, Scopus database, Embase and Cochrane Library Database was conducted. Published studies comparing the prognosis in patients with BCa stratified by HER2 status were included, and relationships between HER2 positivity and gender, stage, grade, lymph node metastasis and survival were analysed.

Results

Nine studies with 2,242 eligible patients were identified. HER2 expression was significantly correlated with poor disease-specific survival [pooled hazard ratio (HR) 2.00; 95 % confidence interval (CI) 1.22–3.29; P = 0.006] and disease-free survival (pooled HR 1.68; 95 % CI 1.33–2.14; P < 0.0001) of patients with BCa. The positive rates of HER2 ranged from 27.8 to 85.2 % with a pooled positive rate of 41.2 % (1,006/2,442). HER2 expression was significantly associated with tumour grade [high grade vs. low grade: odds ratio (OR) 4.08; 95 % CI 1.29–12.93] and lymph node metastasis (positive vs. negative: OR 1.71; 95 % CI 1.07–2.75).

Conclusions

This meta-analysis indicated that HER2 expression is associated with poor prognosis. Thus, HER2 could serve as a useful biomarker for clinical prediction.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29

    Article  PubMed  Google Scholar 

  2. Cho KS, Seo HK, Joung JY, Park WS, Ro JY, Han KS, Chung J, Lee KH (2009) Lymphovascular invasion in transurethral resection specimens as predictor of progression and metastasis in patients with newly diagnosed T1 bladder urothelial cancer. J Urol 182(6):2625–2630

    Article  PubMed  Google Scholar 

  3. Stein JP, Skinner DG (2006) Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure. World J Urol 24(3):296–304

    Article  PubMed  Google Scholar 

  4. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkio S, Flander M, Helle L, Ingalsuo S, Johansson K, Jaaskelainen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J (2006) Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354(8):809–820

    Article  CAS  PubMed  Google Scholar 

  5. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697

    Article  CAS  PubMed  Google Scholar 

  6. Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Uehara T, Fujimoto M, Tsuruyama T, Date H, Haga H (2014) HER2 status in lung adenocarcinoma: a comparison of immunohistochemistry, fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations. Lung Cancer. doi:10.1016/j.lungcan.2014.06.007

  7. Bahmani B, Guerrero Y, Bacon D, Kundra V, Vullev VI, Anvari B (2014) Functionalized polymeric nanoparticles loaded with indocyanine green as theranostic materials for targeted molecular near infrared fluorescence imaging and photothermal destruction of ovarian cancer cells. Lasers Surg Med. doi:10.1002/lsm.22269

  8. Drecoll E, Nitsche U, Bauer K, Berezowska S, Slotta-Huspenina J, Rosenberg R, Langer R (2014) Expression analysis of heat shock protein 90 (HSP90) and Her2 in colon carcinoma. Int J Colorectal Dis 29(6):663–671

    Article  PubMed  Google Scholar 

  9. Ettl T, Stiegler C, Zeitler K, Agaimy A, Zenk J, Reichert TE, Gosau M, Kuhnel T, Brockhoff G, Schwarz S (2012) EGFR, HER2, survivin, and loss of pSTAT3 characterize high-grade malignancy in salivary gland cancer with impact on prognosis. Hum Pathol 43(6):921–931

    Article  CAS  PubMed  Google Scholar 

  10. Zhau HE, Zhang X, von EAC, Scorsone K, Babaian RJ, Ro JY, Hung MC (1990) Amplification and expression of the c-erb B-2/neu proto-oncogene in human bladder cancer. Mol Carcinog 3(5):254–257

    Article  CAS  PubMed  Google Scholar 

  11. Cancer Genome Atlas Research Network (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492):315–322

  12. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16

    Article  PubMed Central  PubMed  Google Scholar 

  13. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605

    Article  PubMed  Google Scholar 

  14. Choi YH, Ahn JH, Kim SB, Jung KH, Gong GY, Kim MJ, Son BH, Ahn SH, Kim WK (2009) Tissue microarray-based study of patients with lymph node-negative breast cancer shows that HER2/neu overexpression is an important predictive marker of poor prognosis. Ann Oncol 20(8):1337–1343

    Article  CAS  PubMed  Google Scholar 

  15. O’Sullivan CC, Swain SM (2013) Pertuzumab: evolving therapeutic strategies in the management of HER2-overexpressing breast cancer. Expert Opin Biol Ther 13(5):779–790

    Article  PubMed  Google Scholar 

  16. Schneider SA, Sukov WR, Frank I, Boorjian SA, Costello BA, Tarrell RF, Thapa P, Houston TR, Tollefson MK, Jeffrey KR, Cheville JC (2014) Outcome of patients with micropapillary urothelial carcinoma following radical cystectomy: ERBB2 (HER2) amplification identifies patients with poor outcome. Mod Pathol 27(5):758–764

    Article  CAS  PubMed  Google Scholar 

  17. Bolenz C, Shariat SF, Karakiewicz PI, Ashfaq R, Ho R, Sagalowsky AI, Lotan Y (2010) Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int 106(8):1216–1222

    Article  PubMed  Google Scholar 

  18. Kolla SB, Seth A, Singh MK, Gupta NP, Hemal AK, Dogra PN, Kumar R (2008) Prognostic significance of Her2/neu overexpression in patients with muscle invasive urinary bladder cancer treated with radical cystectomy. Int Urol Nephrol 40(2):321–327

    Article  PubMed  Google Scholar 

  19. Kruger S, Weitsch G, Buttner H, Matthiensen A, Bohmer T, Marquardt T, Sayk F, Feller AC, Bohle A (2002) Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. Int J Oncol 21(5):981–987

    PubMed  Google Scholar 

  20. Fleischmann A, Rotzer D, Seiler R, Studer UE, Thalmann GN (2011) Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol 60(2):350–357

    Article  CAS  PubMed  Google Scholar 

  21. Gandour-Edwards R, Lara PN Jr, Folkins AK, LaSalle JM, Beckett L, Li Y, Meyers FJ, DeVere-White R (2002) Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma. Cancer 95(5):1009–1015

    Article  CAS  PubMed  Google Scholar 

  22. Ravery V, Grignon D, Angulo J, Pontes E, Montie J, Crissman J, Chopin D (1997) Evaluation of epidermal growth factor receptor, transforming growth factor alpha, epidermal growth factor and c-erbB2 in the progression of invasive bladder cancer. Urol Res 25(1):9–17

    Article  CAS  PubMed  Google Scholar 

  23. Chen PC, Yu HJ, Chang YH, Pan CC (2013) Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression. J Clin Pathol 66(2):113–119

    Article  PubMed  Google Scholar 

  24. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF (2007) 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 131(1):18–43

    CAS  PubMed  Google Scholar 

  25. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF (2014) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138(2):241–256

    Article  PubMed Central  PubMed  Google Scholar 

  26. Tsai YS, Tzai TS, Chow NH, Yang WH, Tong YC, Lin JS, Chang CC, Cheng HL, Lin YM (2003) Prognostic values of p53 and HER-2/neu coexpression in invasive bladder cancer in Taiwan. Urol Int 71(3):262–270

    Article  CAS  PubMed  Google Scholar 

  27. Tsai YS, Tzai TS, Chow NH (2007) Does HER2 immunoreactivity provide prognostic information in locally advanced urothelial carcinoma patients receiving adjuvant M-VEC chemotherapy. Urol Int 79(3):210–216

    Article  CAS  PubMed  Google Scholar 

  28. Rotterud R, Nesland JM, Berner A, Fossa SD (2005) Expression of the epidermal growth factor receptor family in normal and malignant urothelium. BJU Int 95(9):1344–1350

    Article  CAS  PubMed  Google Scholar 

  29. Olsson H, Fyhr IM, Hultman P, Jahnson S (2012) HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder. Scand J Urol Nephrol 46(2):102–107

    Article  CAS  PubMed  Google Scholar 

  30. Simon R, Atefy R, Wagner U, Forster T, Fijan A, Bruderer J, Wilber K, Mihatsch MJ, Gasser T, Sauter G (2003) HER-2 and TOP2A coamplification in urinary bladder cancer. Int J Cancer 107(5):764–772

    Article  CAS  PubMed  Google Scholar 

  31. Jacobs BL, Lee CT, Montie JE (2010) Bladder cancer in 2010: how far have we come. CA Cancer J Clin 60(4):244–272

    Article  PubMed  Google Scholar 

  32. MacLennan GT, Kirkali Z, Cheng L (2007) Histologic grading of noninvasive papillary urothelial neoplasms. Eur Urol 51(4):889–897 discussion 897–898

    Article  PubMed  Google Scholar 

  33. Korkolopoulou P, Christodoulou P, Kapralos P, Exarchakos M, Bisbiroula A, Hadjiyannakis M, Georgountzos C, Thomas-Tsagli E (1997) The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer. Pathol Res Pract 193(11–12):767–775

    Article  CAS  PubMed  Google Scholar 

  34. Chang BS, Kim HL, Yang XJ, Steinberg GD (2001) Correlation between biopsy and radical cystectomy in assessing grade and depth of invasion in bladder urothelial carcinoma. Urology 57(6):1063–1066 discussion 1066–1067

    Article  CAS  PubMed  Google Scholar 

  35. Prinsen CF, Klaassen CH, Thunnissen FB (2003) Microarray as a model for quantitative visualization chemistry. Appl Immunohistochem Mol Morphol 11(2):168–173

    Article  PubMed  Google Scholar 

  36. Cheng L, Davison DD, Adams J, Lopez-Beltran A, Wang L, Montironi R, Zhang S (2014) Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hematol 89(1):73–111

    Article  PubMed  Google Scholar 

  37. Behnsawy HM, Miyake H, Abdalla MA, Sayed MA, Ael-F A, Fujisawa M (2011) Expression of cell cycle-associated proteins in non-muscle-invasive bladder cancer: correlation with intravesical recurrence following transurethral resection. Urol Oncol 29(5):495–501

    Article  CAS  PubMed  Google Scholar 

  38. Janane A, Hajji F, Ismail TO, Elondo JC, Ghadouane M, Ameur A, Abbar M, Bouzidi A (2011) Evaluation of HER2 protein overexpression in non-muscle-invasive bladder cancer with emphasis on tumour grade and recurrence. Actas Urol Esp 35(4):189–194

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China

    Junjie Zhao, Weidong Xu, Zhensheng Zhang, Ruixiang Song, Shuxiong Zeng, Yinghao Sun & Chuanliang Xu

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  1. Junjie Zhao
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  2. Weidong Xu
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  3. Zhensheng Zhang
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Correspondence to Chuanliang Xu.

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Zhao, J., Xu, W., Zhang, Z. et al. Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis. Int Urol Nephrol 47, 87–94 (2015). https://doi.org/10.1007/s11255-014-0866-z

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  • DOI: https://doi.org/10.1007/s11255-014-0866-z

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