Francesco Soria1,2, Marco Moschini1,3, Andrea Haitel4, Gregory J Wirth1,5, Jose A Karam6, Christopher G Wood6, Morgan Rouprêt7, Vitaly Margulis8, Pierre I Karakiewicz9, Alberto Briganti3, Jay D Raman10, Solene-Florence Kammerer-Jacquet11, Romain Mathieu12, Karim Bensalah12, Yair Lotan8, Mehmet Özsoy1, Mesut Remzi1,13, Kilian M Gust1, Shahrokh F Shariat14,15,16. 1. Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. 2. Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy. 3. Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. 4. Department of Pathology, Medical University of Vienna, Vienna, Austria. 5. Geneva Cancer Registry, Global Health Institute, University of Geneva, Geneva, Switzerland. 6. Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 7. Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France. 8. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 9. Department of Urology, University of Montreal, Montreal, Canada. 10. Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA. 11. Department of Pathology, University of Rennes, Rennes, France. 12. Department of Urology, University of Rennes, Rennes, France. 13. Department of Urology, Landeskrankenhaus Weinviertel-Korneuburg, Korneuburg, Austria. 14. Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. shahrokh.shariat@meduniwien.ac.at. 15. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. shahrokh.shariat@meduniwien.ac.at. 16. Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduniwien.ac.at.
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.
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.
Entities:
Keywords:
HER2; Prognosis; UTUC; Upper tract; Urothelial cancer
Authors: Maria Vassilakopoulou; Thibault de la Motte Rouge; Pierre Colin; Adil Ouzzane; David Khayat; Meletios-Athanasios Dimopoulos; Christos A Papadimitriou; Aristotle Bamias; Géraldine Pignot; François Xavier Nouhaud; Sophie Hurel; Laurent Guy; Pierre Bigot; Mathieu Roumiguié; Morgan Rouprêt Journal: Cancer Date: 2011-06-02 Impact factor: 6.860
Authors: Tetsutaro Hayashi; Roland Seiler; Htoo Zarni Oo; Wolfgang Jäger; Igor Moskalev; Shannon Awrey; Takashi Dejima; Tilman Todenhöfer; Na Li; Ladan Fazli; Akio Matsubara; Peter C Black Journal: J Urol Date: 2015-06-03 Impact factor: 7.450
Authors: Richard Zigeuner; Shahrokh F Shariat; Vitaly Margulis; Pierre I Karakiewicz; Marco Roscigno; Alon Weizer; Eiji Kikuchi; Mesut Remzi; Jay D Raman; Christian Bolenz; Karim Bensalah; Umberto Capitanio; Theresa M Koppie; Wassim Kassouf; Kanishka Sircar; Jean-Jacques Patard; Mario I Fernández; Christopher G Wood; Francesco Montorsi; Philipp Ströbel; Jeffery C Wheat; Andrea Haitel; Mototsugu Oya; Charles C Guo; Casey Ng; Daher C Chade; Arthur Sagalowsky; Cord Langner Journal: Eur Urol Date: 2009-11-25 Impact factor: 20.096
Authors: Ilaria Lucca; Wassim Kassouf; Anil Kapoor; Adrian Fairey; Ricardo A Rendon; Jonathan I Izawa; Peter C Black; Harun Fajkovic; Christian Seitz; Mesut Remzi; Peter Nyirády; Morgan Rouprêt; Vitaly Margulis; Yair Lotan; Michela de Martino; Sebastian L Hofbauer; Pierre I Karakiewicz; Alberto Briganti; Giacomo Novara; Shahrokh F Shariat; Tobias Klatte Journal: BJU Int Date: 2015-03-06 Impact factor: 5.588
Authors: Evanguelos Xylinas; Luis Kluth; Niccolo Passoni; Quoc-Dien Trinh; Malte Rieken; Richard K Lee; Harun Fajkovic; Giacomo Novara; Vitaly Margulis; Jay D Raman; Yair Lotan; Morgan Rouprêt; Atiqullah Aziz; Hans-Martin Fritsche; Alon Weizer; Juan I Martinez-Salamanca; Kazumasa Matsumoto; Christian Seitz; Mesut Remzi; Thomas Walton; Pierre I Karakiewicz; Francesco Montorsi; Marc Zerbib; Douglas S Scherr; Shahrokh F Shariat Journal: Eur Urol Date: 2013-09-19 Impact factor: 20.096
Authors: Victor M Schuettfort; Benjamin Pradere; Fahad Quhal; Hadi Mostafaei; Ekaterina Laukhtina; Keiichiro Mori; Reza Sari Motlagh; Michael Rink; David D'Andrea; Mohammad Abufaraj; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Turk J Urol Date: 2020-10-09
Authors: Marco Moschini; David D'Andrea; Stephan Korn; Yasin Irmak; Francesco Soria; Eva Compérat; Shahrokh F Shariat Journal: Nat Rev Urol Date: 2017-09-12 Impact factor: 14.432
Authors: Aurélie Mbeutcha; Romain Mathieu; Morgan Rouprêt; Kilian M Gust; Alberto Briganti; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Transl Androl Urol Date: 2016-10
Authors: Ricardo L Favaretto; Stênio C Zequi; Renato A R Oliveira; Thiago Santana; Walter H Costa; Isabela W Cunha; Gustavo C Guimarães Journal: Int Braz J Urol Date: 2018 Jan-Feb Impact factor: 1.541
Authors: Marco Moschini; Stefania Zamboni; Luca Afferi; Benjamin Pradere; Mohammad Abufaraj; Francesco Soria; David D'Andrea; Morgan Roupret; Alexandre De la Taille; Claudio Simeone; Agostino Mattei; Romain Mathieu; Karim Bensalah; Manfred Peter Wirth; Francesco Montorsi; Alberto Briganti; Andrea Gallina; Giuseppe Simone; Michele Gallucci; Carlo Di Bona; Giancarlo Marra; Andrea Mari; Ettore Di Trapani; Mario Alvarez Maestro; Wojciech Krajewski; Shahrokh F Shariat; Evanguelos Xylinas; Philipp Baumeister Journal: Arab J Urol Date: 2020-09-04
Authors: Hiroshi Fukushima; Baris Turkbey; Peter A Pinto; Aki Furusawa; Peter L Choyke; Hisataka Kobayashi Journal: Cancers (Basel) Date: 2022-06-17 Impact factor: 6.575