Purpose: <br />Reliable and reproducible methods for identifying PD-L1 expression on tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested the reproducibility of the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) tissue samples by pathologists.<br />Experimental Design: <br />NSCLC samples were stained with PD-L1 22C3 pharmDx™ kit using the Dako Autostainer Link 48 Platform. Two sample sets of 60 samples each were designed to assess inter- and intra-observer reproducibility considering 2 cut-points for positivity: 1% or 50% of PD-L1 stained tumor cells. A randomization process was used to obtain equal distribution of PD-L1 positive and negative samples within each sample set. Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all samples on two consecutive days. Subgroup 2 performed the same assessments, except they received a one hour training session prior to the second assessment.<br />Results: <br />For intra-observer reproducibility, the overall percent agreement (OPA) was 89.7% (95%CI: 85.7; 92.6) for the 1% cut-point and 91.3% (95%CI: 87.6; 94.0) for the 50% cut-point. For inter-observer reproducibility, OPA was 84.2% (95%CI: 82.8; 85.5) for the 1% cut-point and 81.9% (95%CI: 80.4; 83.3) for the 50% cut-point, and Cohen's kappa coefficients were 0.68 (95%CI: 0.65; 0.71) and 0.58 (95%CI: 0.55; 0.62), respectively. The training was found to have no or very little impact on intra- or inter-observer reproducibility.<br />Conclusions:<br />Pathologists reported good reproducibility at both 1% and 50% cut-points. More adapted training could potentially increase reliability, in particular for samples with PD-L1 proportion scores around 50%.
- Received January 17, 2017.
- Revision received April 7, 2017.
- Accepted April 11, 2017.
- Copyright ©2017, American Association for Cancer Research.