PD-L1 expression in non-small cell lung carcinoma: Comparison among cytology, small biopsy, and surgical resection specimens

BACKGROUNDOne immunotherapeutic agent for patients with advanced non-small cell lung carcinoma, pembrolizumab, has a companion immunohistochemistry (IHC)-based assay that predicts response by quantifying programmed death-ligand 1 (PD-L1) expression. The current study assessed the feasibility of quantifying PD-L1 expression using cytologic non-small cell lung carcinoma specimens and compared the results with those from small biopsy and surgical resection specimens. METHODSPD-L1 expression was quantified using the IHC-based 22C3 pharmDx assay, with positivity defined as staining in 50% viable tumor cells;100 tumor cells were required for test adequacy. For cytology specimens, IHC was performed on cell block sections. RESULTSA total of 214 specimens were collected from 188 patients, 206 of which (96%) were found to be adequately cellular, including 36 of 40 cytology (90%) and 69 of 72 small biopsy (96%) specimens. There was no significant difference noted with regard to the feasibility of PD-L1 IHC on small biopsy specimens compared with surgical resection specimens (P=.99), or between the percentage of PD-L1-positive cytology and histology (including surgical resection and histologic small biopsy) specimens (P=.083). PD-L1 expression was found to be concordant among samples from 21 of 23 patients from whom>1 specimen was collected (91%). There also was no significant difference observed with regard to rates of PD-L1 positivity when comparing age, sex, diagnosis, and specimen site. CONCLUSIONSQuantification of PD-L1 expression is feasible on cytology specimens, and the results are comparable to those obtained from surgical resection and small biopsy specimens, including in matched specimens and using a single predictive IHC marker. Future studies will be necessary to determine the comparative value of other antibodies and their ability to predict response to immunotherapy. Cancer Cytopathol 2017;125:896-907. (c) 2017 American Cancer Society. Clinical trials of PD-L1 inhibitors currently exclude patients for whom cytologic material only is available for immunohistochemical quantification of PD-L1 expression. Such material is suitable for quantification of PD-L1 expression in samples of non-small cell lung carcinoma.