Heterogeneity of programmed cell death-ligand 1 expression in multifocal lung cancer
A partir de 67 échantillons tumoraux prélevés sur 32 patients atteints de tumeurs multifocales du poumon, cette étude analyse l'hétérogénéité de l'expression de PD-L1 dans ces tumeurs
Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. Since the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers.
Experimental Design: PD-L1 was assessed by immunohistochemistry. Paired lesions were defined as independent primaries or related lesions using mate-pair next-generation sequencing. Agreement statistics were used for analysis.
Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients, and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (kappa=0.01). Sequencing identified that 23 patients had independent primary lung cancers and that nine patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients, and disagreement in 11 patients (kappa=0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients, and disagreement in 1 patient (kappa=0.73).
Conclusions: The expression of PD-L1 is heterogeneous amongst paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis.
Clinical Cancer Research , résumé, 2015