TY - JOUR
T1 - HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)
AU - Soria, Francesco
AU - Moschini, Marco
AU - Haitel, Andrea
AU - Wirth, Gregory J.
AU - Karam, Jose A.
AU - Wood, Christopher G.
AU - Rouprêt, Morgan
AU - Margulis, Vitaly
AU - Karakiewicz, Pierre I.
AU - Briganti, Alberto
AU - Raman, Jay D.
AU - Kammerer-Jacquet, Solene Florence
AU - Mathieu, Romain
AU - Bensalah, Karim
AU - Lotan, Yair
AU - Özsoy, Mehmet
AU - Remzi, Mesut
AU - Gust, Kilian M.
AU - Shariat, Shahrokh F.
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
KW - HER2
KW - Prognosis
KW - UTUC
KW - Upper tract
KW - Urothelial cancer
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U2 - 10.1007/s00345-016-1871-x
DO - 10.1007/s00345-016-1871-x
M3 - Article
C2 - 27272502
AN - SCOPUS:84976323793
SN - 0724-4983
VL - 35
SP - 251
EP - 259
JO - World journal of urology
JF - World journal of urology
IS - 2
ER -