T K Choueiri1, A P Fay2, K P Gray3, M Callea4, T H Ho5, L Albiges2, J Bellmunt6, J Song4, I Carvo4, M Lampron2, M L Stanton5, F S Hodi7, D F McDermott8, M B Atkins9, G J Freeman10, M S Hirsch11, S Signoretti11. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Department of Medical Oncology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston. Electronic address: toni_choueiri@dfci.harvard.edu. 2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston. 3. Biostatistics and Computational Biology, Harvard School of Public Health, Boston. 4. Department of Pathology, Brigham and Women's Hospital, Boston. 5. Department of Medical Oncology, Mayo Clinic, Scottsdale. 6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Department of Medical Oncology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston. 8. Harvard Medical School, Boston; Department of Medical Oncology, Beth-Israel Deaconess Medical Center, Boston. 9. Department of Medical Oncology, Georgetown-Lombardi Comprehensive Cancer Center, Washington, USA. 10. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston. 11. Harvard Medical School, Boston; Department of Pathology, Brigham and Women's Hospital, Boston.
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.
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-L1tumor 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.
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