Expression of PD‐L1 correlates with pleomorphic morphology and histological patterns of non‐small‐cell lung carcinomas

AIMS: As immunomodulatory therapy is being integrated into treatment regimens for non-small-cell lung carcinoma, we aimed to prospectively collect data on the immunohistochemical profile of tumours assessed in our institution and to correlate this with morphological tumour features. METHODS AND RESULTS: Immunohistochemistry for programmed death-ligand 1 (PD-L1) was considered to be adequate when >100 tumour cells were seen microscopically. When adequate, PD-L1 staining was scored as <1%, ≥1-49% or ≥50% positive membrane staining within tumour cells only. There were 197 assessable cases, of which 87% of those with pleomorphic features (n = 39) showed ≥50% positivity for PD-L1 expression, as compared with only 33% of cases without pleomorphic features (P < 0.05) (90% versus 25% in resected cases). Further correlation of PD-L1 expression with architectural patterns within the tumours was performed in 74 adenocarcinoma resections. All invasive mucinous adenocarcinomas scored <1%. All lepidic components in non-mucinous adenocarcinoma resections scored <1%. Thirty-five per cent of the acinar/papillary components and 53% of the solid/micropapillary components were positive for PD-L1 expression. CONCLUSIONS: There are significant differences in PD-L1 expression in relation to histological patterns, with particularly high levels in those with pleomorphic features and low/undetectable levels in invasive mucinous adenocarcinomas and the lepidic components of non-mucinous adenocarcinomas. Assessment of PD-L1 expression in a resected adenocarcinoma with a lepidic component may therefore not be reliable when immumodulatory therapy for recurrent disease is being considered, and either re-biopsy or limiting assessment to the invasive component may be more appropriate.