PD-L1 expression in nonclear-cell renal cell carcinoma

• Published in: Annals of oncology Vol. 25; no. 11; pp. 2178 - 2184
• Main Authors: Choueiri, T.K., Fay, A.P., Gray, K.P., Callea, M., Ho, T.H., Albiges, L., Bellmunt, J., Song, J., Carvo, I., Lampron, M., Stanton, M.L., Hodi, F.S., McDermott, D.F., Atkins, M.B., Freeman, G.J., Hirsch, M.S., Signoretti, S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2014; Oxford University Press
• Series: Editor's choice
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - biosynthesis; B7-H1 Antigen - genetics; benign kidney tumors; Biological and medical sciences; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Female; Gene Expression Regulation, Neoplastic; Humans; immunotherapy; Kidneys; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Nephrology. Urinary tract diseases; nonclear-cell renal cell carcinoma; Original; PD-1 inhibitors; PD-L1; Pharmacology. Drug treatments; renal cell carcinoma; Survival Analysis; Tumors; Tumors of the urinary system; Young Adult; PD-L1; renal cell carcinoma; PD-1 inhibitors; benign kidney tumors; nonclear-cell renal cell carcinoma; immunotherapy; Kidney disease; Urinary system disease; Carcinoma; Kidney tumor; Programmed cell death protein 1; Malignant tumor; Gene expression; In vitro; Treatment; Immunotherapy; Kidney cancer; Grawitz tumor; Inhibitor; Benign neoplasm; Cell adhesion molecule L1; Cancer
• ISSN: 0923-7534; 1569-8041; 1569-8041
• DOI: 10.1093/annonc/mdu445

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