Concordance of PD‐1 and PD‐L1 (B7‐H1) in paired primary and metastatic clear cell renal cell carcinoma

• Published in: Cancer medicine (Malden, MA) MA), 2020-02, Vol.9 (3), p.1152-1160
• Main Authors: Eckel‐Passow, Jeanette E., Ho, Thai H., Serie, Daniel J., Cheville, John C., Houston Thompson, R., Costello, Brian A., Dong, Haidong, Kwon, Eugene D., Leibovich, Bradley C., Parker, Alexander S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Agreements; Apoptosis; B7-H1; B7-H1 Antigen - genetics; Biomarkers; Biomarkers, Tumor - genetics; Cancer Biology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - secondary; Carcinoma, Renal Cell - surgery; ccRCC; Clear cell-type renal cell carcinoma; Discordance; Female; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Kidney - pathology; Kidney - surgery; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Lymphocytes; Male; Metastasectomy; Metastases; Metastasis; Middle Aged; Nephrectomy; Original Research; Pathology; Patients; PD-1; PD-1 protein; PD-L1; PD-L1 protein; Programmed Cell Death 1 Receptor - genetics; RCC; Survival Analysis; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2769

Objectives Previous studies noted discordance of programmed death‐1 (PD‐1) and one of its ligands (PD‐L1) across patient‐matched primary and metastatic clear cell renal cell carcinoma (ccRCC). There are inconsistencies if the primary or metastatic tumor has higher expression, and whether metastatic tumor expression is associated with patient outcome. Thus, we examined PD‐1 and PD‐L1 in patient‐matched tumors using a large number of ccRCC patients with long follow‐up. Materials and Methods We analyzed PD‐1 and PD‐L1 using immunohistochemistry in patient‐matched primary and metastatic tumors from 110 ccRCC patients. Concordance was assessed among longitudinal metastatic tumors, as well as across patient‐matched primary and metastatic tumors. Cox proportional hazards regression was used to evaluate the associations of metastatic tumor expression with cancer‐specific survival. Results We observed inter‐metastatic tumor heterogeneity of PD‐1 in 25 (69%) of the 36 patients and of PD‐L1 in seven (19%) patients. Concordance between patient‐matched primary and metastatic tumors was 73% (Kappa = 0.16, 95% CI: −0.003‐0.32). Similarly, concordance of PD‐L1 between metastatic and patient‐matched primary tumors was 78% (Kappa = 0.27, 95% CI: 0.09‐0.46). Both markers demonstrated higher expression in primary vs metastatic tumors. Metastatic tumor expression of PD‐1 was significantly associated with metastatic location (P