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 Craig
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
N1 - Publisher Copyright:
© 2017 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
PY - 2017/12/1
Y1 - 2017/12/1
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 recurrencefree, 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 0.9e2.16, 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 recurrencefree, 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 0.9e2.16, 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.
KW - Biomarkers
KW - Carcinoma
KW - Lymphocytes, tumor-infiltrating
KW - Programmed cell death 1 receptor
KW - Urinary tract
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U2 - 10.1016/j.juro.2017.06.086
DO - 10.1016/j.juro.2017.06.086
M3 - Article
C2 - 28668287
AN - SCOPUS:85028937742
SN - 0022-5347
VL - 198
SP - 1253
EP - 1262
JO - Journal of Urology
JF - Journal of Urology
IS - 6
ER -