PD-L1 expression in nonclear-cell renal cell carcinoma

Abstract

Background: Programmed death ligand-1 (PD-L1) expression in nonclear-cell RCC (non-ccRCC) and its association with clinical outcomes are unknown.

Methods: Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 101 patients with non-ccRCC. PD-L1 expression was evaluated by immunohistochemistry in both tumor cell membrane and tumor-infiltrating mononuclear cells (TIMC). PD-L1 tumor positivity was defined as ≥5% tumor cell membrane staining. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrate and percentage of positive cells was used. Baseline clinico-pathological characteristics and outcome data [time to recurrence (TTR) and overall survival (OS)] were correlated with PD-L1 staining.

Results: Among 101 patients, 11 (10.9%) were considered PD-L1+ in tumor cells: 2/36 (5.6%) of chromophobe RCC, 5/50 (10%) of papillary RCC, 3/10 (30%) of Xp11.2 translocation RCC and 1/5 (20%) of collecting duct carcinoma. PD-L1 positivity (PD-L1+) in tumor cells was significantly associated with higher stage (P = 0.01) and grade (P = 0.03), as well as shorter OS (P < 0.001). On the other hand, PD-L1 positivity by TIMC was observed in 57 (56.4%) patients: 13/36 (36.1%) of chromophobe RCC, 30/50 (60%) of papillary RCC, 9/10 (90%) of Xp11.2 translocation RCC and 5/5 (100%) of collecting duct carcinoma. A trend toward shorter OS was observed in patients with PD-L1+ in TIMC (P = 0.08). PD-L1+ in both tumor cell membrane and TIMC cells were associated with shorter TTR (P = 0.02 and P = 0.03, respectively).

Conclusion: In non-ccRCC, patients with PD-L1+ tumors appear to have worse clinical outcomes, although only PD-L1 positivity in tumor cells is associated with higher tumor stage and grade.

Keywords: PD-1 inhibitors; PD-L1; benign kidney tumors; immunotherapy; nonclear-cell renal cell carcinoma; renal cell carcinoma.

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

PD-L1 expression in FFPE samples stained with anti-PD-L1 antibody (clone 405.9A11). (A) Positive cell line control; (B) Negative cell line control; (C) Chromophobe RCC; (D) Papillary RCC. (E, F) Xp11.2 translocation RCC. Positive staining is present in tumor cells membrane in panels (C), (D) and (E). In panel (F), tumor cells are negative and tumor-infiltrating immune cells are positive for PD-L1.

Figure 2.

(A) Correlation of PD-L1 expression and OS (univariate analysis) in non-ccRCC; (B) Correlation of PD-L1 expression and TTR (univariate analysis) in non-ccRCC.