Skip to main content

Advertisement

Log in

Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi-quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (HER2) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3–282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (N = 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (≥30 %) micropapillary morphology (N = 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (P = 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with ≥30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629–13.714) for CSS (P = 0.004). CISH revealed HER2 gene amplification in 3/10 tumours with ≥30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  2. Moch H, Humphrey P, Ulbright TM, Reuter VE (eds) (2016) WHO classification of tumours of the urinary system and male genital organs, 4th edn. IARC Press, Lyon

    Google Scholar 

  3. Lopez-Beltran A, Requena MJ, Alvarez-Kindelan J, Quintero A, Blanca A, Montironi R (2007) Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry. J Clin Pathol 60:332–335

    Article  PubMed  Google Scholar 

  4. Alvarado-Cabrero I, Sierra-Santiesteban FI, Mantilla-Morales A, Hernández-Hernandez DM (2005) Micropapillary carcinoma of the urothelial tract. A clinicopathologic study of 38 cases. Ann Diagn Pathol 9:1–5

    Article  PubMed  Google Scholar 

  5. Johansson SL, Borghede G, Holmäng S (1999) Micropapillary bladder carcinoma: a clinicopathological study of 20 cases. J Urol 161:1798–1802

    Article  CAS  PubMed  Google Scholar 

  6. Alkibay T, Sözen S, Gürocak S, Işik Gönül I, Poyraz A, Ure I (2009) Micropapillary pattern in urothelial carcinoma: a clinicopathological analysis. Urol Int 83:300–305

    Article  PubMed  Google Scholar 

  7. Ghoneim IA, Miocinovic R, Stephenson AJ, et al. (2011) Neoadjuvant systemic therapy or early cystectomy? Single-center analysis of outcomes after therapy for patients with clinically localized micropapillary urothelial carcinoma of the bladder. Urology 77:867–870

    Article  PubMed  Google Scholar 

  8. Kamat AM, Gee JR, Dinney CP, et al. (2006) The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma. J Urol 175:881–885

    Article  PubMed  Google Scholar 

  9. Compérat E, Roupret M, Yaxley J, et al. (2010) Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 72 cases. Pathology 42:650–654

    Article  PubMed  Google Scholar 

  10. Fairey AS, Daneshmand S, Wang L, et al. (2014) Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy. Urol Oncol 32:110–116

    Article  PubMed  Google Scholar 

  11. Willis DL, Porten SP, Kamat AM (2013) Should histologic variants alter definitive treatment of bladder cancer? Curr Opin Urol 23:435–443

    Article  PubMed  Google Scholar 

  12. Perepletchikov AM, Parwani AV (2009) Micropapillary urothelial carcinoma: Clinico-pathologic review. Pathol Res Pract 205:807–810

    Article  PubMed  Google Scholar 

  13. Witjes JA, Compérat E, Cowan NC, et al. (2014) EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 65:778–792

    Article  PubMed  Google Scholar 

  14. Willis DL, Flaig TW, Hansel DE, et al. (2014) Micropapillary bladder cancer: current treatment patterns and review of the literature. Urol Oncol 32(6):826–832

    Article  PubMed  PubMed Central  Google Scholar 

  15. Meeks JJ, Taylor JM, Matsushita K, Herr HW, Donat SM, Bochner BH, Dalbagni G (2013) Pathological response to neoadjuvant chemotherapy for muscle-invasive micropapillary bladder cancer. BJU Int 111:E325–E330

    Article  PubMed  Google Scholar 

  16. Krause FS, Walter B, Ott OJ, et al. (2011) 15-year survival rates after transurethral resection and radiochemotherapy or radiation in bladder cancer treatment. Anticancer Res 31:985–990

    PubMed  Google Scholar 

  17. Ching CB, Amin MB, Tubbs RR, et al. (2011) HER2 gene amplification occurs frequently in the micropapillary variant of urothelial carcinoma: analysis by dual-color in situ hybridization. Mod Pathol 24:1111–1119

    Article  CAS  PubMed  Google Scholar 

  18. Schneider SA, Sukov WR, Frank I, et al. (2014) Outcome of patients with micropapillary urothelial carcinoma following radical cystectomy: ERBB2 (HER2) amplification identifies patients with poor outcome. Mod Pathol 27:758–764

    Article  CAS  PubMed  Google Scholar 

  19. Tschui J, Vassella E, Bandi N, et al. (2015) Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer. Virchows Arch 466:703–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wittekind C, Meyer HJ (eds) (2010) Klassifikation maligner Tumoren. 7th Edn. Wiley-VCH, Weinheim

  21. Mostofi FK, Sobin LH, Torloni H (1973) Histological classification of urinary bladder tumours. In: Histological typing of urinary bladder tumours. International Classification of Tumours, No 10. Geneva: World Health Organisation;1973

  22. Wolff AC, Hammond ME, Hicks DG, et al. (2013) 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. J Clin Oncol 31:3997–4013

    Article  PubMed  Google Scholar 

  23. Amin MB, Ro JY, el-Sharkawy T, et al. (1994) Micropapillary variant of transitional cell carcinoma of the urinary bladder. Histologic pattern resembling ovarian papillary serous carcinoma. Am J Surg Pathol 18:1224–1232

    Article  CAS  PubMed  Google Scholar 

  24. Kamat AM, Dinney CP, Gee JR, et al. (2007) Micropapillary bladder cancer: a review of the university of Texas M. D. Anderson cancer center experience with 100 consecutive patients. Cancer 110:62–67

    Article  PubMed  Google Scholar 

  25. Mak RH, Hunt D, Shipley WU, et al. (2014) Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 32:3801–3809

    Article  PubMed  PubMed Central  Google Scholar 

  26. James ND, Hussain SA, Hall E, et al. (2012) Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 366:1477–1488

    Article  CAS  PubMed  Google Scholar 

  27. Sangoi AR, Beck AH, Amin MB, et al. (2010) Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol 34:1367–1376

    Article  PubMed  Google Scholar 

  28. Sangoi AR, Higgins JP, Rouse RV, Schneider AG, McKenney JK (2009) Immunohistochemical comparison of MUC1, CA125, and her2neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact. Mod Pathol 22:660–667

    Article  CAS  PubMed  Google Scholar 

  29. Samaratunga H, Khoo K (2004) Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study. Histopathology 45:55–64

    Article  CAS  PubMed  Google Scholar 

  30. Masson-Lecomte A, Xylinas E, Bouquot M, et al. (2015) Oncological outcomes of advanced muscle-invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum-based chemotherapy. World J Urol 33:1087–1093

    Article  CAS  PubMed  Google Scholar 

  31. McQuitty E, Ro JY, Truong LD, Shen SS, Zhai Q, Ayala AG (2012) Lymphovascular invasion in micropapillary urothelial carcinoma: a study of 22 cases. Arch Pathol Lab Med 136:635–639

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful for the excellent technical support given by the laboratory staff of the Department of Pathology at the University Hospital Erlangen, in particular Rudolf Jung, Ute Zimmermann and Christa Winkelmann.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Simone Bertz.

Ethics declarations

Prior institutional review board (University Hospital Erlangen, Germany) approval was obtained for the analysis on archival material (Reference-No. 4434).

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bertz, S., Wach, S., Taubert, H. et al. Micropapillary morphology is an indicator of poor prognosis in patients with urothelial carcinoma treated with transurethral resection and radiochemotherapy. Virchows Arch 469, 339–344 (2016). https://doi.org/10.1007/s00428-016-1986-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-016-1986-x

Keywords

Navigation