HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC).
OBJECTIVE
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.
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.|Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Francesco
F
Soria
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.|Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
Marco
M
Moschini
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Andrea
A
Haitel
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.|Geneva Cancer Registry, Global Health Institute, University of Geneva, Geneva, Switzerland.
Gregory J
GJ
Wirth
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Jose A
JA
Karam
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Christopher G
CG
Wood
Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France.
Morgan
M
Rouprêt
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Vitaly
V
Margulis
Department of Urology, University of Montreal, Montreal, Canada.
Pierre I
PI
Karakiewicz
Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
Alberto
A
Briganti
Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
Jay D
JD
Raman
Department of Pathology, University of Rennes, Rennes, France.
Solene-Florence
SF
Kammerer-Jacquet
Department of Urology, University of Rennes, Rennes, France.
Romain
R
Mathieu
Department of Urology, University of Rennes, Rennes, France.
Karim
K
Bensalah
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yair
Y
Lotan
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Mehmet
M
Özsoy
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.|Department of Urology, Landeskrankenhaus Weinviertel-Korneuburg, Korneuburg, Austria.
Mesut
M
Remzi
Department of Urology, Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Kilian M
KM
Gust
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.|Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. shahrokh.shariat@meduniwien.ac.at.|Department of Urology, Weill Cornell Medical College, New York, NY, USA. shahrokh.shariat@meduniwien.ac.at.
Shahrokh F
SF
Shariat
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014516:Ureteral Neoplasms / Q000235:genetics* / Q000401:mortality
HER2; Prognosis; UTUC; Upper tract; Urothelial cancer