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

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 Raman, Solene Florence Kammerer-Jacquet, Romain Mathieu, Karim Bensalah, Yair Lotan, Mehmet Özsoy, Mesut Remzi, Kilian M. Gust, Shahrokh F. Shariat

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalWorld Journal of Urology
Volume35
Issue number2
DOIs
StatePublished - Feb 1 2017

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Carcinoma
Neoplasms
Recurrence
Multicenter Studies
Necrosis
Retrospective Studies
Lymph Nodes
Immunohistochemistry
Staining and Labeling
Neoplasm Metastasis
Membranes
Mortality
Therapeutics

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Soria, F., Moschini, M., Haitel, A., Wirth, G. J., Karam, J. A., Wood, C. G., ... Shariat, S. F. (2017). HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). World Journal of Urology, 35(2), 251-259. https://doi.org/10.1007/s00345-016-1871-x
Soria, Francesco ; Moschini, Marco ; Haitel, Andrea ; Wirth, Gregory J. ; Karam, Jose A. ; Wood, Christopher G. ; Rouprêt, Morgan ; Margulis, Vitaly ; Karakiewicz, Pierre I. ; Briganti, Alberto ; Raman, Jay ; Kammerer-Jacquet, Solene Florence ; Mathieu, Romain ; Bensalah, Karim ; Lotan, Yair ; Özsoy, Mehmet ; Remzi, Mesut ; Gust, Kilian M. ; Shariat, Shahrokh F. / HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). In: World Journal of Urology. 2017 ; Vol. 35, No. 2. pp. 251-259.
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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.",
author = "Francesco Soria and Marco Moschini and Andrea Haitel and Wirth, {Gregory J.} and Karam, {Jose A.} and Wood, {Christopher G.} and Morgan Roupr{\^e}t and Vitaly Margulis and Karakiewicz, {Pierre I.} and Alberto Briganti and Jay Raman and Kammerer-Jacquet, {Solene Florence} and Romain Mathieu and Karim Bensalah and Yair Lotan and Mehmet {\"O}zsoy and Mesut Remzi and Gust, {Kilian M.} and Shariat, {Shahrokh F.}",
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Soria, F, Moschini, M, Haitel, A, Wirth, GJ, Karam, JA, Wood, CG, Rouprêt, M, Margulis, V, Karakiewicz, PI, Briganti, A, Raman, J, Kammerer-Jacquet, SF, Mathieu, R, Bensalah, K, Lotan, Y, Özsoy, M, Remzi, M, Gust, KM & Shariat, SF 2017, 'HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)', World Journal of Urology, vol. 35, no. 2, pp. 251-259. https://doi.org/10.1007/s00345-016-1871-x

HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). / Soria, Francesco; Moschini, Marco; Haitel, Andrea; Wirth, Gregory J.; Karam, Jose A.; Wood, Christopher G.; Rouprêt, Morgan; Margulis, Vitaly; Karakiewicz, Pierre I.; Briganti, Alberto; Raman, Jay; Kammerer-Jacquet, Solene Florence; Mathieu, Romain; Bensalah, Karim; Lotan, Yair; Özsoy, Mehmet; Remzi, Mesut; Gust, Kilian M.; Shariat, Shahrokh F.

In: World Journal of Urology, Vol. 35, No. 2, 01.02.2017, p. 251-259.

Research output: Contribution to journalArticle

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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

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.

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.

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