Expression of PD-1 and PD-L1 in patients with renal cell carcinoma with sarcomatoid dedifferentiation (sRCC).

Abstract

582 Background: sRCC is a very aggressive malignancy, with limited treatment options. Given the recent surge in novel immunotherapeutic agents targeting PD-1 and PD-L1, we decided to investigate the expression of these markers in patients with sRCC. Methods: PD-1 and PD-L1 immunohistochemistry was performed on whole sections from nephrectomy specimens in 118 patients with sRCC and 92 patients with clear cell RCC without sarcomatoid dedifferentiation(ccRCC). PD-1 staining was manually evaluated. PD-1 cell numbers ≥ 1/HPF was defined as positive. PD-L1 staining was evaluated with semiquantitative method (H-score = 0-300) with digital analysis. Results: Of the 118 patients with sRCC, 94 had clear cell epithelioid component and 24 had non-clear cell epithelioid component. In the cohort with ccRCC, 20 were grade 4, 58 were grade 3, and 14 were grade 2. 21 cases of sRCC that received neoadjuvant therapy and 2 sRCC and 1 ccRCC where digitally calculated H-score was at variance with manual evaluation were eliminated from the study. 98.6% (73/74) of clear cell sRCC were positive for PD-1. Similarly, 100% (20/20) of the non-clear cell sRCC, 95% (19/20) of the grade 4, and 55/58 (94.8%) of grade 3 ccRCC were positive for PD-1, whereas 9/14 (64.3%) of the grade 2 ccRCC expressed PD-1 (P= 0.0002). 43.2% (32/74) of clear cell sRCC and 55.0% (11/20) of the non-clear cell sRCC were positive for PD-L1, whereas only 10% of the grade 4 non-sarcomatoid ccRCC were positive for PD-L1 (P= 0.0047). None of the grade 2 and 3 ccRCC expressed PD-L1. All the PD-L1 positive cases except 1 clear cell sRCC case were also PD-1 positive. We found a threshold H-score ≥ 25 in sRCC to stratify patient groups with worse prognosis (P= 0.0435) with 29.3% of the cases showing H-score ≥ 25. High PD-L1 H-score was significantly associated with presence of metastatic disease (P= 0.0284). Conclusions: sRCC (both clear and non-clear cell) showed higher frequency and stronger expression of PD-L1 and higher PD-1 positive cell density compared to ccRCC without sarcomatoid component. High expression of PD-L1 is at significant risk of cancer related mortality for sRCC patients. These findings form a rationale to study PD-1 and PD-L1 targeting agents in patients with sRCC.