Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Malte Rieken, Shahrokh F. Shariat, Jose A. Karam, Beat Foerster, Francesca Khani, Kilian Gust, Mohammad Abufaraj, Christopher G. Wood, Alon Z. Weizer, Jay Raman, Charles C. Guo, Nathalie Rioux-Leclercq, Andrea Haitel, Karim Bensalah, Yair Lotan, Alexander Bachmann, Angelo M. De Marzo, Brian D. Robinson, Vitaly Margulis

Research output: Contribution to journalArticle

Abstract

Purpose To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. Materials and Methods We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. Results PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09–2.61, p = 0.02). Conclusions In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.

Original languageEnglish (US)
Pages (from-to)1269-1277
Number of pages9
JournalJournal of Urology
Volume198
Issue number6
DOIs
StatePublished - Dec 1 2017

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PTEN Phosphohydrolase
Carcinoma
Mortality
Recurrence
Lymph Nodes
Regression Analysis
Staining and Labeling
Neoplasm Metastasis
Neoplasms
Proportional Hazards Models
Monoclonal Antibodies
Survival

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Rieken, Malte ; Shariat, Shahrokh F. ; Karam, Jose A. ; Foerster, Beat ; Khani, Francesca ; Gust, Kilian ; Abufaraj, Mohammad ; Wood, Christopher G. ; Weizer, Alon Z. ; Raman, Jay ; Guo, Charles C. ; Rioux-Leclercq, Nathalie ; Haitel, Andrea ; Bensalah, Karim ; Lotan, Yair ; Bachmann, Alexander ; De Marzo, Angelo M. ; Robinson, Brian D. ; Margulis, Vitaly. / Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy. In: Journal of Urology. 2017 ; Vol. 198, No. 6. pp. 1269-1277.
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title = "Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy",
abstract = "Purpose To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. Materials and Methods We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. Results PTEN staining was absent in 45 cases (7.4{\%}). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95{\%} CI 1.09–2.61, p = 0.02). Conclusions In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.",
author = "Malte Rieken and Shariat, {Shahrokh F.} and Karam, {Jose A.} and Beat Foerster and Francesca Khani and Kilian Gust and Mohammad Abufaraj and Wood, {Christopher G.} and Weizer, {Alon Z.} and Jay Raman and Guo, {Charles C.} and Nathalie Rioux-Leclercq and Andrea Haitel and Karim Bensalah and Yair Lotan and Alexander Bachmann and {De Marzo}, {Angelo M.} and Robinson, {Brian D.} and Vitaly Margulis",
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Rieken, M, Shariat, SF, Karam, JA, Foerster, B, Khani, F, Gust, K, Abufaraj, M, Wood, CG, Weizer, AZ, Raman, J, Guo, CC, Rioux-Leclercq, N, Haitel, A, Bensalah, K, Lotan, Y, Bachmann, A, De Marzo, AM, Robinson, BD & Margulis, V 2017, 'Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy', Journal of Urology, vol. 198, no. 6, pp. 1269-1277. https://doi.org/10.1016/j.juro.2017.06.096

Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy. / Rieken, Malte; Shariat, Shahrokh F.; Karam, Jose A.; Foerster, Beat; Khani, Francesca; Gust, Kilian; Abufaraj, Mohammad; Wood, Christopher G.; Weizer, Alon Z.; Raman, Jay; Guo, Charles C.; Rioux-Leclercq, Nathalie; Haitel, Andrea; Bensalah, Karim; Lotan, Yair; Bachmann, Alexander; De Marzo, Angelo M.; Robinson, Brian D.; Margulis, Vitaly.

In: Journal of Urology, Vol. 198, No. 6, 01.12.2017, p. 1269-1277.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Frequency and Prognostic Value of PTEN Loss in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

AU - Rieken, Malte

AU - Shariat, Shahrokh F.

AU - Karam, Jose A.

AU - Foerster, Beat

AU - Khani, Francesca

AU - Gust, Kilian

AU - Abufaraj, Mohammad

AU - Wood, Christopher G.

AU - Weizer, Alon Z.

AU - Raman, Jay

AU - Guo, Charles C.

AU - Rioux-Leclercq, Nathalie

AU - Haitel, Andrea

AU - Bensalah, Karim

AU - Lotan, Yair

AU - Bachmann, Alexander

AU - De Marzo, Angelo M.

AU - Robinson, Brian D.

AU - Margulis, Vitaly

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Purpose To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. Materials and Methods We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. Results PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09–2.61, p = 0.02). Conclusions In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.

AB - Purpose To our knowledge the frequency and prognostic significance of PTEN protein expression in upper tract urothelial carcinoma have not yet been investigated in large studies. We analyzed PTEN protein status and its association with disease recurrence and survival outcomes in a large, multi-institutional upper tract urothelial carcinoma cohort. Materials and Methods We retrospectively analyzed the records of 611 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy between 1991 and 2008 at a total of 7 institutions. Median followup was 23 months. Tissue microarrays and immunohistochemical PTEN staining (monoclonal antibody) were performed. Univariable and multivariable Cox regression models were created to address the association of PTEN protein expression with disease recurrence, and cancer specific and overall mortality. Results PTEN staining was absent in 45 cases (7.4%). Patients with PTEN loss had significantly advanced pathological tumor stage and grade (p <0.001), and higher rates of lymph node metastasis (p <0.01) and lymphovascular invasion (p <0.001) compared to patients with PTEN expression. PTEN loss was associated with disease recurrence, and cancer specific and overall mortality on univariable Cox regression analyses. However, on multivariable Cox regression analyses adjusted for the effect of standard clinicopathological features PTEN loss was only associated with overall mortality (HR 1.69, 95% CI 1.09–2.61, p = 0.02). Conclusions In patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma loss of PTEN protein expression is rare but associated with features of biologically aggressive disease such as higher grade and stage as well as lymph node metastasis. Loss of PTEN expression was associated with overall mortality. PTEN loss seemed to promote worse outcomes in this relatively small group of patients.

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