Abstract
BackgroundTo 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.MethodsInterpretation 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.ResultsUsing 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).ConclusionsPD-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0925-6) contains supplementary material, which is available to authorized users.
Highlights
To date, there are no effective therapeutic targeting agents for triple-negative breast cancer (TNBC), and programmed death (PD)-L1 has presented potential as an effective marker of immunotherapeutic agents
PD‐L1 monoclonal antibody staining in TNBC cells and immune cells Among the different PD-L1 monoclonal antibodies, PD-L1 (E1L3N) showed the highest expression rate in cancer cells (14.7, 14.7, 11.0, 2.3 %) and immune cells (37.6 %) and PD-L1 (SP142) showed the lowest expression rate in cancer cells (11.5, 11.0, 6.9, 0.5 %) and immune cells (19.3 %) for all cut-off values (1, 5, 10, and 50 %) (Table 2; Fig. 1)
In conclusion, staining with PD-L1, PD-L1, and PD-L1 monoclonal antibodies in cancer cells and immune cells varied, with the highest staining by PD-L1 (E1L3N) and the lowest by PD-L1 (SP142)
Summary
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. Breast cancer is a heterogeneous disease that has several clinical, histological, and genetic forms. There have been many attempts to categorize this heterogeneous disease, Among these molecular subtypes, basal-like breast cancer has a more aggressive clinical course than other subtypes and is commonly known as triple-negative breast cancer (TNBC), which is defined clinically as lacking estrogen receptor (ER) and progesterone receptor. PD-L1 was expressed in tumor cells but immune cells in previous studies of breast cancer [22,23,24], and lung cancer [25]. The evaluation of PD-L1 should be performed in both cancer cell and immune cells
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