Background: To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and PD-L1 has presented potential as an effective marker of immunotherapeutic agents. The aim of this study was to evaluate the expression of PD-L1 by three different immunohistochemical antibodies in TNBC. Methods: Interpretation of all three PD-L1 antibodies showed good concordance among three readers (kappa value >0.610) in both cancer cells and immune cells. Using a tissue microarray (TMA) constructed from 218 cases of TNBC, we performed immunohistochemical staining using three of the most popular commercially used PD-L1 monoclonal antibodies (clones 28-8, E1L3N and SP142) in cancer cells and immune cells. Results: Using various cut-off values of previous studies (1, 5, 10 and 50 %), the expression rates in cancer cells were: PD-L1 (E1L3N) (14.7, 14.7, 11.0, 2.3 %), PD-L1 (28-8) (13.3, 12.4, 10.1, 1.8 %), and PD-L1 (SP142) (11.5, 11.0, 6.9, 0.5 %), respectively. At the 5 % cut-off value, the discordance rate among the three antibodies was 6.0-10.6 % and was highest between PD-L1 (SP142) and the other two antibodies. The expression rates in immune cells were PD-L1 (E1L3N) (37.6 %), PD-L1 (28-8) (36.7 %), and PD-L1 (SP142) (19.3 %), and the discordance rate among the three antibodies ranged from 13.8 to 24.8 % and was also highest between PD-L1 (SP142) and the other two antibodies. Among stromal histologic types, higher PD-L1 expression in cancer cells and immune cells was measured in inflammatory-type (p < 0.05). The absence of PD-L1 (28-8) staining in immune cells was associated with shorter disease free survival (DFS) and overall survival (OS) (p = 0.043, and p = 0.021) in univariate analyses, and with shorter OS in multivariate Cox analysis (hazard ratio: 5.429, 95 % CI 1.214-24.28, p = 0.027). Conclusions: PD-L1 detection in cancer cells and immune cells varied by antibody clone. The greatest amount of staining occurred with PD-L1 (E1L3N), followed by PD-L1 (28-8) and PD-L1 (SP142). The concordance rate among monoclonal PD-L1 antibodies was higher between PD-L1 (28-8) and PD-L1 (E1L3N). To determine the gold standard antibody and the most appropriate cut-off value, further study of the clinical trial group treated with PD-L1 inhibitor is necessary.
Bibliographical noteFunding Information:
This study was supported by a Grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1420080). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209).
© 2016 The Author(s)
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)