Comparative Study of PD-L1 Status between Surgically Resected Specimens and Matched Biopsies of Gastric Cancer Reveal Major Discordances: A Potential Issue for Anti-PD-L1 Therapeutic Strategies

Abstract

Background: Inhibitors of programmed death-ligand 1 (PD-L1) have potential therapeutic value in gastric cancer. We investigated PD-L1 expression patterns in paired biopsy and resection specimens. Patients and Methods: Thirty-nine formalin-fixed, paraffin-embedded paired samples were assessed using PD-L1 22C3 pharmDx immunohistochemistry technique. Combined positive score (CPS) was calculated as the ratio of PD-L1 stained cells (tumor cells, lymphocytes, and macrophages) to the total number of viable tumor cells, multiplied by 100. The CPS ≥1 indicated PD-L1 positivity. Results: PD-L1 positivity was evident for 33 (84.6%) of 39 resection cases; all displayed low positivity (1≤CPS<50). Only 10 (30.3%) of 33 positive cases in the resection specimens had simultaneous PD-L1 positivity in the paired biopsy specimens; two cases displayed high positivity (CPS 50 and 70) and eight displayed low positivity (1≤CPS≤50). Among the 29 negative cases with biopsy specimens, 23 (79.3%) displayed PD-L1 low positivity in the paired resection specimens and only six had concordant negativity in both specimens with poor agreement (concordance rate 41.0%, k value = 0.118, correlation coefficient 0.234; p=0.152). All the high microsatellite instability cases had concordant PD-L1 positivity in resection and biopsy specimens. Conclusions: There was relatively poor agreement of PD-L1 expression between biopsy and resected tumor specimens. The biopsy specimens underestimated the PD-L1 status observed for the total resected samples. This indicates the necessity of obtaining multiple biopsies from different areas of the tumor to enhance the validity and reliability of PD-L1 analysis.