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HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)

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Abstract

Purpose

The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes.

Methods

This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed.

Results

HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage (p < 0.001), presence of lymph node metastasis (p = 0.006), high-grade tumor (p < 0.001), tumor necrosis (p = 0.01) and lymphovascular invasion (p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24–2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21–1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33–2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence (p = 0.04), overall (p = 0.02) and cancer-specific mortality (p = 0.02).

Conclusions

Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors.

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Authors’ contribution

V. Margulis, Y. Lotan and S.F. Shariat were involved in protocol/project development. A. Haitel, J.A. Karam, C.G. Wood, M. Rouprêt, V. Margulis, P.I. Karakiewicz, A. Briganti, J.D. Raman, S.-F. Kammerer-Jacquet, R. Mathieu, K. Bensalah, Y. Lotan, M. Özsoy, M. Remzi, K.M. Gust and S.F. Shariat were involved in data collection or management. F. Soria, M. Moschini, G.J. Wirth and S.F. Shariat were involved in data analysis. F. Soria, M. Moschini, G.J. Wirth and S.F. Shariat wrote and edited the manuscript. F. Soria, M. Moschini, G.J. Wirth, A. Haitel, J.A. Karam, C.G. Wood, M. Rouprêt, V. Margulis, P.I. Karakiewicz, A. Briganti, J.D. Raman, S.-F. Kammerer-Jacquet, R. Mathieu, K. Bensalah, Y. Lotan, M. Özsoy, M. Remzi, K.M. Gust and S.F. Shariat edited the manuscript.

Author information

Authors and Affiliations

  1. Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Francesco Soria, Marco Moschini, Gregory J. Wirth, Mehmet Özsoy, Mesut Remzi, Kilian M. Gust & Shahrokh F. Shariat

  2. Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy

    Francesco Soria

  3. Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy

    Marco Moschini & Alberto Briganti

  4. Department of Pathology, Medical University of Vienna, Vienna, Austria

    Andrea Haitel

  5. Geneva Cancer Registry, Global Health Institute, University of Geneva, Geneva, Switzerland

    Gregory J. Wirth

  6. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Vitaly Margulis, Yair Lotan & Shahrokh F. Shariat

  7. Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Jose A. Karam & Christopher G. Wood

  8. Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France

    Morgan Rouprêt

  9. Department of Urology, University of Montreal, Montreal, Canada

    Pierre I. Karakiewicz

  10. Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA

    Jay D. Raman

  11. Department of Pathology, University of Rennes, Rennes, France

    Solene-Florence Kammerer-Jacquet

  12. Department of Urology, University of Rennes, Rennes, France

    Romain Mathieu & Karim Bensalah

  13. Department of Urology, Landeskrankenhaus Weinviertel-Korneuburg, Korneuburg, Austria

    Mesut Remzi

  14. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

Authors
  1. Francesco Soria
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  2. Marco Moschini
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  3. Andrea Haitel
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  4. Gregory J. Wirth
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  5. Jose A. Karam
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  6. Christopher G. Wood
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  7. Morgan Rouprêt
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  8. Vitaly Margulis
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  9. Pierre I. Karakiewicz
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  10. Alberto Briganti
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  11. Jay D. Raman
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  12. Solene-Florence Kammerer-Jacquet
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  13. Romain Mathieu
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  14. Karim Bensalah
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  15. Yair Lotan
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  16. Mehmet Özsoy
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  17. Mesut Remzi
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  18. Kilian M. Gust
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  19. Shahrokh F. Shariat
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Corresponding author

Correspondence to Shahrokh F. Shariat.

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Conflict of interest

I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript, are the following: Shahrokh Shariat owns or co-owns the following patents: Methods to determine prognosis after therapy for prostate cancer. Granted 2002-09-06. Methods to determine prognosis after therapy for bladder cancer. Granted 2003-06-19. Prognostic methods for patients with prostatic disease. Granted 2004-08-05. Soluble Fas: urinary marker for the detection of bladder transitional cell carcinoma. Granted 2010-07-20. He is advisory board member of Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanofi and Wolff. He is speaker for Astellas, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi and Wolff. The other authors made no disclosures.

Ethical standard

This was an institutional review board-approved study, with all participating sites providing the necessary institutional data use agreements before initiation of the study.

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Soria, F., Moschini, M., Haitel, A. et al. HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). World J Urol 35, 251–259 (2017). https://doi.org/10.1007/s00345-016-1871-x

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  • DOI: https://doi.org/10.1007/s00345-016-1871-x

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