Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies

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.

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

“…The comparison between different commercially available PD‐L1 antibodies revealed a general good concordance in BC, especially between Ventana SP263, Dako 22c3, and rbMCAL10, and between Dako 28‐8 and E1L3N . However, comparative analyses of different PD‐L1 antibodies on NSCLC tissue samples consistently reported low sensitivity of SP142 antibody, because it was associated with significantly lower rates of PD‐L1 detection on both tumor and immune cells .…”

“…Several studies evaluated PD‐L1 expression according to baseline clinicopathological features of patients with BC, consistently reporting a correlation between higher PD‐L1 expression and unfavorable classic prognostic factors, particularly poorer histological grade , higher proliferative index , more advanced N stage , larger tumor size , and younger age at BC diagnosis .…”

“…In particular, PD‐L1 expression has been positively and independently associated with DFS/RFS and/or OS in several unselected primary BC cohorts . In addition, when considering specific BC subtypes, it has been suggested that PD‐L1 protein expression may retain a positive prognostic role in TNBC and in HER2+ BC, in both trastuzumab‐treated and untreated patients .…”

“…In addition, the adoption of different scoring systems and thresholds for PD‐L1 positivity may contribute to further reducing the reproducibility of PD‐L1 assessment. Indeed, in BC, discordant results were reported when different positivity cutoffs were applied and when tumor cells and tumor‐infiltrating immune cells were differentially considered .…”

Immunotherapy for Breast Cancer: Current and Future Strategies

“…The presence of both markers has been identified on tumor cells and tumor infiltrating lymphocytes, especially in triple-negative breast cancers. However, the clinical and prognostic predictive values of the PD-1 axis have been mixed [60-63]. The presence of other ICRs like TIGIT and LAG-3 noted in breast cancer (Table 1) may also play important roles in shaping the immune-tumor interface in breast cancer.…”