862PPD-L1 EXPRESSION IN MUSCLE-INVASIVE BLADDER CANCER CYSTECTOMY SPECIMENS AND LYMPH NODE METASTASIS

2014 
ABSTRACT Aim: The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has been shown to play an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or it's ligand PD-L1 have demonstrated promising clinical activity against several solid tumor types. Preliminary data have suggested a relationship between PD-L1 expression on tumor cells and objective response. Immunological responses in bladder cancer are known to be relatively well preserved with immunotherapy routinely used for early disease. We sought to investigate the frequency of PD-L1 overexpression in muscle-invasive bladder cancer cystectomy specimens and lymph nodes metastasis to investigate the feasibility of using this as a biomarker to select patients for PD-1/ PD-L1 directed therapy. Methods: Cases of radical cystectomy for muscle-invasive bladder cancer were identified from pathology records at our institution. Representative slides from archived tumor blocks were incubated with anti-PD-L1 antibody (clone 5H1). PD-L1 positivity was defined by a 5% expression threshold. Results: 54 radical cystectomy specimens with muscle-invasive bladder cancer were reviewed. Patient characteristics: female 4/54, male 50/54, median age 69 (range 30-88). Tumor characteristics: 100% high-grade transitional cell carcinoma, pT2 19/54 (35%), pT3 31/54 (57%), pT4 4/54 (7%), pN1 17/54 (31%). PD-L1 was overexpressed in 5/54 cases (9%), all of these cases were at least pT3a. Of 4/5 PD-L1 positive cases with associated lymph node metastasis, corresponding overexpression of PD-L1 was seen in only 2 of these 4 specimens. Conclusions: PD-L1 was overexpressed in 9% of muscle-invasive bladder cancer cystectomy specimens in this cohort with corresponding PD-L1 overexpression in the lymph node metastasis of only 2 of 4 cases with lymph node metastatic disease. Disclosure: D. Mukherji: Honoraria and travel support recieved from Sanofi and Janssen. All other authors have declared no conflicts of interest.
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