Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract

Laura Maria Krabbe, Aditya Bagrodia, Ahmed Q. Haddad, Payal Kapur, Dina Khalil, Linda S. Hynan, Christopher G. Wood, Jose A. Karam, Alon Z. Weizer, Jay Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Shahrokh F. Shariat, Yair Lotan, Vitaly Margulis

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Abstract

Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.

Original languageEnglish (US)
Pages (from-to)1486-1493
Number of pages8
JournalJournal of Urology
Volume193
Issue number5
DOIs
StatePublished - May 1 2015

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Urinary Tract
Carcinoma
Survival
Neoplasms
Recurrence
Multivariate Analysis
Carcinoma in Situ
Kaplan-Meier Estimate
Necrosis
Lymph Nodes
Staining and Labeling
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Krabbe, Laura Maria ; Bagrodia, Aditya ; Haddad, Ahmed Q. ; Kapur, Payal ; Khalil, Dina ; Hynan, Linda S. ; Wood, Christopher G. ; Karam, Jose A. ; Weizer, Alon Z. ; Raman, Jay ; Remzi, Mesut ; Rioux-Leclercq, Nathalie ; Haitel, Andrea ; Roscigno, Marco ; Bolenz, Christian ; Bensalah, Karim ; Sagalowsky, Arthur I. ; Shariat, Shahrokh F. ; Lotan, Yair ; Margulis, Vitaly. / Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract. In: Journal of Urology. 2015 ; Vol. 193, No. 5. pp. 1486-1493.
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abstract = "Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20{\%}. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2{\%} of patients were male. Ki-67 was over expressed in 25.9{\%} of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95{\%} CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95{\%} CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.",
author = "Krabbe, {Laura Maria} and Aditya Bagrodia and Haddad, {Ahmed Q.} and Payal Kapur and Dina Khalil and Hynan, {Linda S.} and Wood, {Christopher G.} and Karam, {Jose A.} and Weizer, {Alon Z.} and Jay Raman and Mesut Remzi and Nathalie Rioux-Leclercq and Andrea Haitel and Marco Roscigno and Christian Bolenz and Karim Bensalah and Sagalowsky, {Arthur I.} and Shariat, {Shahrokh F.} and Yair Lotan and Vitaly Margulis",
year = "2015",
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language = "English (US)",
volume = "193",
pages = "1486--1493",
journal = "Journal of Urology",
issn = "0022-5347",
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Krabbe, LM, Bagrodia, A, Haddad, AQ, Kapur, P, Khalil, D, Hynan, LS, Wood, CG, Karam, JA, Weizer, AZ, Raman, J, Remzi, M, Rioux-Leclercq, N, Haitel, A, Roscigno, M, Bolenz, C, Bensalah, K, Sagalowsky, AI, Shariat, SF, Lotan, Y & Margulis, V 2015, 'Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract', Journal of Urology, vol. 193, no. 5, pp. 1486-1493. https://doi.org/10.1016/j.juro.2014.11.007

Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract. / Krabbe, Laura Maria; Bagrodia, Aditya; Haddad, Ahmed Q.; Kapur, Payal; Khalil, Dina; Hynan, Linda S.; Wood, Christopher G.; Karam, Jose A.; Weizer, Alon Z.; Raman, Jay; Remzi, Mesut; Rioux-Leclercq, Nathalie; Haitel, Andrea; Roscigno, Marco; Bolenz, Christian; Bensalah, Karim; Sagalowsky, Arthur I.; Shariat, Shahrokh F.; Lotan, Yair; Margulis, Vitaly.

In: Journal of Urology, Vol. 193, No. 5, 01.05.2015, p. 1486-1493.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multi-institutional validation of the predictive value of Ki-67 in patients with high grade urothelial carcinoma of the upper urinary tract

AU - Krabbe, Laura Maria

AU - Bagrodia, Aditya

AU - Haddad, Ahmed Q.

AU - Kapur, Payal

AU - Khalil, Dina

AU - Hynan, Linda S.

AU - Wood, Christopher G.

AU - Karam, Jose A.

AU - Weizer, Alon Z.

AU - Raman, Jay

AU - Remzi, Mesut

AU - Rioux-Leclercq, Nathalie

AU - Haitel, Andrea

AU - Roscigno, Marco

AU - Bolenz, Christian

AU - Bensalah, Karim

AU - Sagalowsky, Arthur I.

AU - Shariat, Shahrokh F.

AU - Lotan, Yair

AU - Margulis, Vitaly

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.

AB - Purpose We validate the independent predictive value of Ki-67 in patients with high grade upper tract urothelial carcinoma. Materials and Methods A total of 475 patients from the international Upper Tract Urothelial Carcinoma Collaboration who underwent extirpative surgery for high grade upper tract urothelial carcinoma were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray formed from this patient cohort. Ki-67 expression was assessed in a semiquantitative fashion and considered over expressed at a cutoff of 20%. Multivariate analyses were performed to assess independent predictors of oncologic outcomes and Harrell's C indices were calculated for predictive models. Results The median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was over expressed in 25.9% of patients. Ki-67 over expression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ and regional lymph node metastases. On Kaplan-Meier analyses over expressed Ki-67 was associated with worse recurrence-free survival (HR 12.6, p <0.001) and cancer specific survival (HR 15.8, p <0.001). On multivariate analysis Ki-67 was an independent predictor of recurrence-free survival (HR 1.6, 95% CI 1.07-2.30, p=0.021) and cancer specific survival (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved Harrell's C index from 0.66 to 0.70 (p <0.0001) for recurrence-free survival as well as cancer specific survival in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for recurrence-free survival and 0.81 to 0.83 (p=0.005) for cancer specific survival in our postoperative model. Conclusions Ki-67 was validated as an independent predictor of recurrence-free survival and cancer specific survival in patients treated with extirpative surgery for high grade upper tract urothelial carcinoma in a large, multi-institutional cohort.

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