Expression of PD-L1 in primary urothelial carcinoma (UC).

Abstract

4541 Background: Engagement of programmed cell death-1 (PD-1), expressed on CD8+ T cells, with it ligand PD-L1(B7H1), expressed on tumor cells, results in T cell suppression and tumor protection. Antibodies against PD-1 or PD-L1 have reported impressive anti-tumor activities in phase I/II trials and are being tested in the phase 3 setting. Exploratory analysis indicated that expression of PD-L1 could be a predictive marker for response. Of note, urothelial carcinoma (UC) was not included in the early phase anti-PD1 or anti-PD-L1 studies. To explore anti-PD-L1 as a new treatment for this lethal disease, we assessed PD-L1 expression in UC. Methods: The relative mRNA abundance of PD-L1 mRNA in UC was studied in the Oncomine Bittner Multi-cancer dataset, which included a total of 1911 tumor samples. PD-L1 immunohistochemistry (IHC) was performed with rabbit monoclonal antibody against human PD-L1 on tissue microarrays with 83 formalin fixed paraffin embedded T1, T2 and T3 UC. IHC slides were reviewed by a genitourinary pathologist. A positive staining is defined when ≥ 5% of cancer cells had positive PD-L1 membrane and/or cytoplasmic staining. The IHC slides were scanned with the Aperio ScanScope XT and the immunopositivity of PD-L1 was quantitatively scored using commercial algorithms from the Aperio Toolbox and TissueStudio. The 1+, 2+, and 3+ score of each core was based on the dominant IHC staining intensity. Results: In the Bittner multi-cancer dataset, the log2 median mRNA intensities of PD-L1 in prostate cancer, clear cell renal cell carcinoma, colon cancer, UC of the bladder, ureter and squamous cell carcinoma of the bladder were 0.245, 0.528, 0.61, 0.81, 0.802, and 1.202 respectively. The overall PD-L1 IHC staining positivity was 45% in 83 primary UC samples. All six 3+ PD-L1 staining cores were grade 3 urothelial carcinomas and each core had more than 60% of cancer cells with 3+ PD-L1 membrane staining. Grade 3 cores also had the highest percentage of 2+ and 3+ PD-L1 positivity. No association was observed between T staging and PD-L1 staining intensity. Conclusions: PD-L1 is expressed in primary UC. We have obtained additional UC samples to correlate its expression with survival and its expression pattern with the pattern of tumor infiltrating lymphocytes.