Abstract
Purpose: Response to anti-PD-L1/PD-1 immunotherapy correlates with PD-L1 expression in breast cancer. However, the prevalence of PD-L1 positive breast cancer is variable, which could be due to differences in the population/cohort of patients tested or the preservation/detection technology used. To investigate this variability, we examined the effect of two tissue preservation methods on PD-L1 immunohistochemical detection in breast cancer. Methods: We compared PD-L1 expression in patient-matched frozen (FR) and formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer patients. PD-L1 expression was assessed using tumor proportion score (TPS, simply PD-L1 score), and case positivity was determined with PD-L1 score ≥5. Results: In FFPE tissues, PD-L1 was positive in 7–10% of tested patients, depending on the antibody used. In patient-matched FR tissues, the same antibodies showed positive PD-L1 expression in 20–30% of cases. The impact of the antibody tested on the rate of PD-L1 positivity (% of PDL1 positive cases) was minor, as evident in the near perfect concordance between PD-L1 score obtained using the different antibodies whether tested in FR or FFPE tissues. However, there was a systematic drop by an average of 13–20% in the PD-L1 score obtained in FFPE tissues compared to their patient-matched FR tissues. Conclusions: In the tested patient-matched cohort, there was consistently a higher PD-L1 score in FR than FFPE tissues, regardless of the antibody used, demonstrating a significant effect on PD-L1 detection due to the preservation method. These findings should inspire further work to improve the sensitivity of PD-L1 detection and possibly search for more sensitive antibodies in FFPE tissues.
Highlights
Programmed death-ligand 1 (PD-L1) is a T-cell inhibitory molecule that is expressed on antigen-presenting cells (APC), leading to the induction of T-cell anergy and/or apoptosis [1]
We have further tested the correlation of PD-L1 expression obtained with SP263 antibody in formalin-fixed paraffin-embedded (FFPE) tissues with hormone receptor status of breast cancer, known prognostic markers to correlate with PD-L1 expression in breast cancer
We found that PD-L1 obtained with SP263 antibody in FFPE tissues correlated with estrogen and progesterone receptornegative status in a similar fashion to what was previously reported with the MIH1 antibody in FR tissues (Table 1)
Summary
Programmed death-ligand 1 (PD-L1) is a T-cell inhibitory molecule that is expressed on antigen-presenting cells (APC), leading to the induction of T-cell anergy and/or apoptosis [1]. PD-L1 is aberrantly overexpressed in most malignancies (reviewed in [2]) to promote their immune escape, and therapies against PD-L1 showed unprecedented response rates in cancer patients (reviewed in [3]). The status of PD-L1 expression correlates with a positive response to anti-PD-L1 therapy [4]. We and others have previously demonstrated the expression of PD-L1 in breast cancer and its correlation with well-known poor prognostic factors [6,7]. There was considerable variability between studies in the prevalence of PD-L1 positive cases in breast cancer. It remains to be determined whether this is due to differences in the population/cohort of patients tested or the preservation/detection technology used
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call