Abstract 994P
Background
PD-L1 testing is currently performed by immunohistochemical (IHC) analysis of PD-L1-positive cells. We questioned whether the results of PCR-based measurement of PD-L1 RNA expression correlate with IHC scores obtained by different commercial assays.
Methods
167 consecutive non-squamous non-small cell lung carcinomas (NSCLCs) were analyzed for PD-L1 RNA expression and subjected to 22C3, SP263 and SP142 IHC scoring using recommended cut-offs.
Results
RNA and protein expression measurements demonstrated good correlation as continuous variables, however there were discrepancies relative to standard thresholds. PCR-based assay had excellent negative predictive value towards the cut-off of 1% stained tumor cells, given that absent/low RNA expression was observed in 51/52 (98%) and 48/52 (92%) NSCLCs negative by 22C3 and SP263 IHC staining, respectively. Moderate/high PD-L1 RNA expression was registered in 115/167 (69%) cases, while only 64 (56%) of these 115 NSCLCs had expression in more than 1% tumor cells. Among the remaining 51 tumors, 17 (33%) NSCLCs expressed PD-L1 in >/=1% immune cells, 26 (51%) showed PD-L1 staining in 0.1-0.9% tumors cells and 8 (16%) cases were entirely negative by IHC. Similarly, PCR assays showed excellent capability to reveal tumors with <50% stained tumor cells (22C3: 133/139 (96%); SP263: 131/139 (94%)) or with <50% stained tumor cells and <10% stained immune cells (SP142: 137/139 (99%)), however provided insufficient specificity in identifying tumors with IHC PD-L1 expression above these clinically accepted thresholds. 22C3 and SP263 antibodies, which are believed to be interchangeable, showed concordant results for 145/167 (87%) and 162/167 (97%) tumors for 1% and 50% cut-offs, respectively.
Conclusions
Some NSCLCs demonstrate readily detectable PD-L1 expression on the level of RNA, but fall below commonly accepted cut-offs by IHC. It remains to be studied whether these discrepancies are attributed to technical or biological reasons. Clinical sensitivity of these tumors to immune therapy deserves additional investigations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study has been supported by the Russian Science Foundation (grant 20-15-00244).
Disclosure
All authors have declared no conflicts of interest.