Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma

Laura Maria Krabbe, Barbara Heitplatz, Sina Preuss, Ryan C. Hutchinson, Solomon L. Woldu, Nirmish Singla, Martin Boegemann, Christopher G. Wood, Jose A. Karam, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Leonid M. Rapoport, Peter V. Glybochko, Marco Roscigno, Christian Bolenz, Karim Bensalah, Arthur I. SagalowskyShahrokh F. Shariat, Yair Lotan, Evanguelos Xylinas, Vitaly Margulis

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Abstract

Purpose: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. Materials and Methods: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. Results: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

Original languageEnglish (US)
JournalJournal of Urology
DOIs
StateAccepted/In press - Jan 1 2017

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Carcinoma
Survival
Tumor-Infiltrating Lymphocytes
Multivariate Analysis
Recurrence
Neoplasms
Immunohistochemistry
Staining and Labeling
Antibodies

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Krabbe, L. M., Heitplatz, B., Preuss, S., Hutchinson, R. C., Woldu, S. L., Singla, N., ... Margulis, V. (Accepted/In press). Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma. Journal of Urology. https://doi.org/10.1016/j.juro.2017.06.086
Krabbe, Laura Maria ; Heitplatz, Barbara ; Preuss, Sina ; Hutchinson, Ryan C. ; Woldu, Solomon L. ; Singla, Nirmish ; Boegemann, Martin ; Wood, Christopher G. ; Karam, Jose A. ; Weizer, Alon Z. ; Raman, Jay D. ; Remzi, Mesut ; Rioux-Leclercq, Nathalie ; Haitel, Andrea ; Rapoport, Leonid M. ; Glybochko, Peter V. ; Roscigno, Marco ; Bolenz, Christian ; Bensalah, Karim ; Sagalowsky, Arthur I. ; Shariat, Shahrokh F. ; Lotan, Yair ; Xylinas, Evanguelos ; Margulis, Vitaly. / Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma. In: Journal of Urology. 2017.
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title = "Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma",
abstract = "Purpose: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. Materials and Methods: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N{\circledR} via immunohistochemistry. A 1{\%} or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. Results: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2{\%} and 26.2{\%} of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95{\%} CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95{\%} CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95{\%} CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95{\%} CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95{\%} CI 0.11-0.63, p = 0.003). Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.",
author = "Krabbe, {Laura Maria} and Barbara Heitplatz and Sina Preuss and Hutchinson, {Ryan C.} and Woldu, {Solomon L.} and Nirmish Singla and Martin Boegemann and Wood, {Christopher G.} and Karam, {Jose A.} and Weizer, {Alon Z.} and Raman, {Jay D.} and Mesut Remzi and Nathalie Rioux-Leclercq and Andrea Haitel and Rapoport, {Leonid M.} and Glybochko, {Peter V.} and Marco Roscigno and Christian Bolenz and Karim Bensalah and Sagalowsky, {Arthur I.} and Shariat, {Shahrokh F.} and Yair Lotan and Evanguelos Xylinas and Vitaly Margulis",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.juro.2017.06.086",
language = "English (US)",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",

}

Krabbe, LM, Heitplatz, B, Preuss, S, Hutchinson, RC, Woldu, SL, Singla, N, Boegemann, M, Wood, CG, Karam, JA, Weizer, AZ, Raman, JD, Remzi, M, Rioux-Leclercq, N, Haitel, A, Rapoport, LM, Glybochko, PV, Roscigno, M, Bolenz, C, Bensalah, K, Sagalowsky, AI, Shariat, SF, Lotan, Y, Xylinas, E & Margulis, V 2017, 'Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma', Journal of Urology. https://doi.org/10.1016/j.juro.2017.06.086

Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma. / Krabbe, Laura Maria; Heitplatz, Barbara; Preuss, Sina; Hutchinson, Ryan C.; Woldu, Solomon L.; Singla, Nirmish; Boegemann, Martin; Wood, Christopher G.; Karam, Jose A.; Weizer, Alon Z.; Raman, Jay D.; Remzi, Mesut; Rioux-Leclercq, Nathalie; Haitel, Andrea; Rapoport, Leonid M.; Glybochko, Peter V.; Roscigno, Marco; Bolenz, Christian; Bensalah, Karim; Sagalowsky, Arthur I.; Shariat, Shahrokh F.; Lotan, Yair; Xylinas, Evanguelos; Margulis, Vitaly.

In: Journal of Urology, 01.01.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma

AU - Krabbe, Laura Maria

AU - Heitplatz, Barbara

AU - Preuss, Sina

AU - Hutchinson, Ryan C.

AU - Woldu, Solomon L.

AU - Singla, Nirmish

AU - Boegemann, Martin

AU - Wood, Christopher G.

AU - Karam, Jose A.

AU - Weizer, Alon Z.

AU - Raman, Jay D.

AU - Remzi, Mesut

AU - Rioux-Leclercq, Nathalie

AU - Haitel, Andrea

AU - Rapoport, Leonid M.

AU - Glybochko, Peter V.

AU - Roscigno, Marco

AU - Bolenz, Christian

AU - Bensalah, Karim

AU - Sagalowsky, Arthur I.

AU - Shariat, Shahrokh F.

AU - Lotan, Yair

AU - Xylinas, Evanguelos

AU - Margulis, Vitaly

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Purpose: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. Materials and Methods: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. Results: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

AB - Purpose: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. Materials and Methods: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. Results: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

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