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.
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.
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).
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.
World journal of urology. 2016 Jun 07 [Epub ahead of print]
Francesco Soria, Marco Moschini, Andrea Haitel, Gregory J Wirth, Jose A Karam, Christopher G Wood, Morgan Rouprêt, Vitaly Margulis, Pierre I Karakiewicz, Alberto Briganti, Jay D Raman, Solene-Florence Kammerer-Jacquet, Romain Mathieu, Karim Bensalah, Yair Lotan, Mehmet Özsoy, Mesut Remzi, Kilian M Gust, Shahrokh F Shariat
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Pathology, Medical University of Vienna, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Urology, University of Montreal, Montreal, Canada., Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy., Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA., Department of Pathology, University of Rennes, Rennes, France., Department of Urology, University of Rennes, Rennes, France., Department of Urology, University of Rennes, Rennes, France., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria., Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. .