Inter and intra-tumor heterogeneity of PD-L1 and MET expression in metastatic renal cell carcinoma (mRCC).

Abstract

4569 Background: Although inhibition of PD-1/PD-L1 and MET receptors have clinical efficacy in mRCC, their expression is not a predictive biomarker. Heterogeneity between the sites of disease might be one explanation. The aim of our study was to evaluate PD-L1 and MET expression in primary and metastases (brain (BM)/pancreas (PM)) RCC lesions and their correlation with clinicopathologic characteristics. Methods: RCC specimen from different institutions were collected. Clinicopathologic characteristics were assessed by revision of samples. PD-L1 and MET expression in tumor cells (TC) and immune cells (IC) ( > 1%) were assessed by immunohistochemistry. Results: 180resected RCC specimen were successful collected (42 primary tumors and 138 metastases (87 BM/51 PM)). Overall, 22%, 51% and 23% of patients had at least one specimen expressing PD-L1 TC, IC and MET, respectively. In primary tumours, the proportion was 12%, 50% and 0%, respectively. In metastasis, the proportion of PD-L1 TC was 22% (23% in BM vs 19% in PM, p = 0.631), PD-L1 IC was 48% (47% in BM vs 49% in PM, p = 0.821) and MET was 24% (35% in BM vs 2% in PM, p < 0.001). Comparing paired samples (primary tumour and metastasis) there was discordances of PD-L1 in TC or IC and of MET expression in 30%, 27% and 24% of samples, respectively. These two first disagreements seem varied over time. The discordance in PD-L1 TC or IC and MET between primary tumor and PM (BM) was 15% (40%), 33% (22%) and 0% (67%), respectively. Some correlations were observed between MET and PD-L1 and clinicopathologic characteristics. Conclusions: In this largest analysis, evaluating heterogeneity between primary tumor and metastases (brain/pancreatic lesions) in mRCC, PD-L1 and MET expression suggests that the assessment as predictive biomarkers may require analysis of metastatic lesions. [Table: see text]