Caveolin-1 Expression in Upper Tract Urothelial Carcinoma

David D'Andrea, Marco Moschini, Beat Foerster, Mohammad Abufaraj, Vitaly Margulis, Jose Karam, Yair Lotan, Jay Raman, Romain Mathieu, Morgan Rouprêt, Pierre I. Karakiewicz, Alberto Briganti, Andrea Haitel, Sharhrokh F. Shariat

Research output: Contribution to journalArticle

Abstract

Background: Improvement in postoperative risk stratification of upper tract urothelial carcinoma (UTUC) is required to better predict outcomes and counsel patients on adjuvant treatment. Objective: To validate the association between caveolin-1 and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for UTUC. Design, setting, and participants: Caveolin-1 expression was evaluated via immunochemistry on a tissue microarray from 621 patients. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positive. The median follow-up in this retrospective study was 35 mo (interquartile range 16-65). Intervention: Radical nephroureterectomy. Outcome measurements and statistical analysis: Univariate and multivariable Cox proportional hazards regression models were used to assess the association between caveolin-1 expression and recurrence and cancer-specific mortality (CSM). Results and limitations: Caveolin-1 was overexpressed in 150 patients (24%). Overexpression was associated with higher pathological stage (p< 0.001) and grade (p< 0.001). In univariate analyses, overexpression of caveolin-1 was significantly associated with lower recurrence (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6; p = 0.004) and CSM (HR 1.8, 95% CI 1.2-2.7; p = 0.005); however, multivariable analyses did not prove its independent association with outcomes. The study is limited by its retrospective nature. Conclusions: Despite overexpression in a quarter of UTUC patients, caveolin-1 was not independently associated with oncological outcomes. Its use could be evaluated to improve clinical staging of biopsy specimens and to help in clinical decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Patient summary: Development of a panel of prognostic and predictive markers is mandatory for patient consultations in the era of personalized medicine. We evaluated the role of caveolin-1 in a large series of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it was not independently associated with oncological outcomes. Nevertheless, it was associated with adverse pathological features. Considering caveolin-1 in UTUC biopsy specimens could help in improving clinical staging and decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Caveolin-1 is associated with worse oncological features among patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), but is not independently associated with oncological outcomes. Its clinical use could be explored in UTUC biopsy specimens for improving clinical staging and helping in decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment.

Original languageEnglish (US)
JournalEuropean Urology Focus
DOIs
StateAccepted/In press - 2017

Fingerprint

Caveolin 1
Carcinoma
Neoadjuvant Therapy
Kidney
Biopsy
Confidence Intervals
Immunochemistry
Recurrence
Neoplasms
Precision Medicine
Mortality
Proportional Hazards Models
Decision Making
Referral and Consultation
Retrospective Studies

Keywords

  • Biomarker
  • Caveolin-1
  • Nephroureterectomy
  • Outcome
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

D'Andrea, D., Moschini, M., Foerster, B., Abufaraj, M., Margulis, V., Karam, J., ... Shariat, S. F. (Accepted/In press). Caveolin-1 Expression in Upper Tract Urothelial Carcinoma. European Urology Focus. https://doi.org/10.1016/j.euf.2017.06.011

Caveolin-1 Expression in Upper Tract Urothelial Carcinoma. / D'Andrea, David; Moschini, Marco; Foerster, Beat; Abufaraj, Mohammad; Margulis, Vitaly; Karam, Jose; Lotan, Yair; Raman, Jay; Mathieu, Romain; Rouprêt, Morgan; Karakiewicz, Pierre I.; Briganti, Alberto; Haitel, Andrea; Shariat, Sharhrokh F.

In: European Urology Focus, 2017.

Research output: Contribution to journalArticle

D'Andrea, D, Moschini, M, Foerster, B, Abufaraj, M, Margulis, V, Karam, J, Lotan, Y, Raman, J, Mathieu, R, Rouprêt, M, Karakiewicz, PI, Briganti, A, Haitel, A & Shariat, SF 2017, 'Caveolin-1 Expression in Upper Tract Urothelial Carcinoma', European Urology Focus. https://doi.org/10.1016/j.euf.2017.06.011
D'Andrea, David ; Moschini, Marco ; Foerster, Beat ; Abufaraj, Mohammad ; Margulis, Vitaly ; Karam, Jose ; Lotan, Yair ; Raman, Jay ; Mathieu, Romain ; Rouprêt, Morgan ; Karakiewicz, Pierre I. ; Briganti, Alberto ; Haitel, Andrea ; Shariat, Sharhrokh F. / Caveolin-1 Expression in Upper Tract Urothelial Carcinoma. In: European Urology Focus. 2017.
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abstract = "Background: Improvement in postoperative risk stratification of upper tract urothelial carcinoma (UTUC) is required to better predict outcomes and counsel patients on adjuvant treatment. Objective: To validate the association between caveolin-1 and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for UTUC. Design, setting, and participants: Caveolin-1 expression was evaluated via immunochemistry on a tissue microarray from 621 patients. Caveolin-1 was considered overexpressed when at least 50{\%} of the tumor cells stained positive. The median follow-up in this retrospective study was 35 mo (interquartile range 16-65). Intervention: Radical nephroureterectomy. Outcome measurements and statistical analysis: Univariate and multivariable Cox proportional hazards regression models were used to assess the association between caveolin-1 expression and recurrence and cancer-specific mortality (CSM). Results and limitations: Caveolin-1 was overexpressed in 150 patients (24{\%}). Overexpression was associated with higher pathological stage (p< 0.001) and grade (p< 0.001). In univariate analyses, overexpression of caveolin-1 was significantly associated with lower recurrence (hazard ratio [HR] 1.7, 95{\%} confidence interval [CI] 1.2-2.6; p = 0.004) and CSM (HR 1.8, 95{\%} CI 1.2-2.7; p = 0.005); however, multivariable analyses did not prove its independent association with outcomes. The study is limited by its retrospective nature. Conclusions: Despite overexpression in a quarter of UTUC patients, caveolin-1 was not independently associated with oncological outcomes. Its use could be evaluated to improve clinical staging of biopsy specimens and to help in clinical decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Patient summary: Development of a panel of prognostic and predictive markers is mandatory for patient consultations in the era of personalized medicine. We evaluated the role of caveolin-1 in a large series of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it was not independently associated with oncological outcomes. Nevertheless, it was associated with adverse pathological features. Considering caveolin-1 in UTUC biopsy specimens could help in improving clinical staging and decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Caveolin-1 is associated with worse oncological features among patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), but is not independently associated with oncological outcomes. Its clinical use could be explored in UTUC biopsy specimens for improving clinical staging and helping in decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment.",
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T1 - Caveolin-1 Expression in Upper Tract Urothelial Carcinoma

AU - D'Andrea, David

AU - Moschini, Marco

AU - Foerster, Beat

AU - Abufaraj, Mohammad

AU - Margulis, Vitaly

AU - Karam, Jose

AU - Lotan, Yair

AU - Raman, Jay

AU - Mathieu, Romain

AU - Rouprêt, Morgan

AU - Karakiewicz, Pierre I.

AU - Briganti, Alberto

AU - Haitel, Andrea

AU - Shariat, Sharhrokh F.

PY - 2017

Y1 - 2017

N2 - Background: Improvement in postoperative risk stratification of upper tract urothelial carcinoma (UTUC) is required to better predict outcomes and counsel patients on adjuvant treatment. Objective: To validate the association between caveolin-1 and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for UTUC. Design, setting, and participants: Caveolin-1 expression was evaluated via immunochemistry on a tissue microarray from 621 patients. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positive. The median follow-up in this retrospective study was 35 mo (interquartile range 16-65). Intervention: Radical nephroureterectomy. Outcome measurements and statistical analysis: Univariate and multivariable Cox proportional hazards regression models were used to assess the association between caveolin-1 expression and recurrence and cancer-specific mortality (CSM). Results and limitations: Caveolin-1 was overexpressed in 150 patients (24%). Overexpression was associated with higher pathological stage (p< 0.001) and grade (p< 0.001). In univariate analyses, overexpression of caveolin-1 was significantly associated with lower recurrence (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6; p = 0.004) and CSM (HR 1.8, 95% CI 1.2-2.7; p = 0.005); however, multivariable analyses did not prove its independent association with outcomes. The study is limited by its retrospective nature. Conclusions: Despite overexpression in a quarter of UTUC patients, caveolin-1 was not independently associated with oncological outcomes. Its use could be evaluated to improve clinical staging of biopsy specimens and to help in clinical decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Patient summary: Development of a panel of prognostic and predictive markers is mandatory for patient consultations in the era of personalized medicine. We evaluated the role of caveolin-1 in a large series of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it was not independently associated with oncological outcomes. Nevertheless, it was associated with adverse pathological features. Considering caveolin-1 in UTUC biopsy specimens could help in improving clinical staging and decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Caveolin-1 is associated with worse oncological features among patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), but is not independently associated with oncological outcomes. Its clinical use could be explored in UTUC biopsy specimens for improving clinical staging and helping in decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment.

AB - Background: Improvement in postoperative risk stratification of upper tract urothelial carcinoma (UTUC) is required to better predict outcomes and counsel patients on adjuvant treatment. Objective: To validate the association between caveolin-1 and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for UTUC. Design, setting, and participants: Caveolin-1 expression was evaluated via immunochemistry on a tissue microarray from 621 patients. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positive. The median follow-up in this retrospective study was 35 mo (interquartile range 16-65). Intervention: Radical nephroureterectomy. Outcome measurements and statistical analysis: Univariate and multivariable Cox proportional hazards regression models were used to assess the association between caveolin-1 expression and recurrence and cancer-specific mortality (CSM). Results and limitations: Caveolin-1 was overexpressed in 150 patients (24%). Overexpression was associated with higher pathological stage (p< 0.001) and grade (p< 0.001). In univariate analyses, overexpression of caveolin-1 was significantly associated with lower recurrence (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.6; p = 0.004) and CSM (HR 1.8, 95% CI 1.2-2.7; p = 0.005); however, multivariable analyses did not prove its independent association with outcomes. The study is limited by its retrospective nature. Conclusions: Despite overexpression in a quarter of UTUC patients, caveolin-1 was not independently associated with oncological outcomes. Its use could be evaluated to improve clinical staging of biopsy specimens and to help in clinical decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Patient summary: Development of a panel of prognostic and predictive markers is mandatory for patient consultations in the era of personalized medicine. We evaluated the role of caveolin-1 in a large series of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) and found that it was not independently associated with oncological outcomes. Nevertheless, it was associated with adverse pathological features. Considering caveolin-1 in UTUC biopsy specimens could help in improving clinical staging and decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment. Caveolin-1 is associated with worse oncological features among patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), but is not independently associated with oncological outcomes. Its clinical use could be explored in UTUC biopsy specimens for improving clinical staging and helping in decision-making regarding a kidney-sparing approach or neoadjuvant systemic treatment.

KW - Biomarker

KW - Caveolin-1

KW - Nephroureterectomy

KW - Outcome

KW - Upper tract urothelial carcinoma

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