Concordance levels of PD-L1 expression by immunohistochemistry, mRNA in situ hybridization, and outcome in lung carcinomas

• Published in: Human pathology 2018-12, Vol.82, p.282-288
• Main Authors: Coppock, Joseph D., Volaric, Ashley K., Mills, Anne M., Gru, Alejandro A.
• Format: Article
• Language: English
• Subjects: Archives & records; Biomarkers; Cancer therapies; Chemotherapy; Concordance; FDA approval; Hybridization; Immunohistochemistry; Lung cancer; Metastasis; Non–small cell lung carcinoma; Pathology; Patients; PD-L1; Protein expression; Proteins; RNA in situ hybridization; Stains & staining; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2018.07.025

Targeted inhibition of programmed cell death-1 (PD-1) and its ligand (PD-L1) has emerged as first-line therapy for advanced non–small cell lung cancer. Although patients with high PD-L1 expression have improved outcomes with anti–PD-1/PD-L1–directed therapies, use as a predictive biomarker is complicated by robust responses in some patients with low-level expression. Furthermore, reported PD-L1 levels in lung cancers vary widely, and discrepancies exist with different antibodies. PD-L1 expression was thus compared by immunohistochemistry (IHC) versus RNA in situ hybridization (ISH) in 112 lung cancers by tissue microarray: 51 adenocarcinoma, 42 squamous cell carcinoma, 9 adenosquamous carcinoma, 5 carcinoid, 3 undifferentiated large cell carcinoma, 1 large cell neuroendocrine carcinoma, and 1 small cell carcinoma. At least 1% tumor cell staining was considered positive in each modality. A positive concordance of only 60% (67/112) was found between IHC and ISH. Fifty percent (56/112) were positive by IHC and 50% (56/112) by ISH; however, 20% (22/112) were ISH positive but IHC negative. Conversely, 21% (23/112) were IHC positive but ISH negative. There was no significant stratification of PD-L1 positivity by histologic subtype. A trend of more PD-L1–positive stage I cancers identified by ISH versus IHC was observed but was not statistically significant (50% [27/54] by IHC and 64% [35/55] by ISH, P = .18). No significant difference in survival was identified, with an average of 5.3 months in IHC versus 5.2 months in ISH-positive cases. The results demonstrate discordance between PD-L1 RNA levels and protein expression in non–small cell lung cancers, warranting comparison as predictive biomarkers. •PD-L1 expression was compared in 112 cases of lung carcinoma by IHC and RNA ISH using a TMA.•A positive concordance of only 60% (67/112) was found between PD-L1 IHC and RNA ISH.•There was no significant stratification of PD-L1 positivity by histologic subtype.•No significant difference in survival was identified in IHC versus RNA ISH positive cases.•The results warrant future comparison of these modalities as predictive biomarkers.