Heterogeneity of PD-L1 expression in lung adenocarcinoma metastasis is related to histopathological subtypes

Objectives: The heterogeneity of PD-L1 expression and its relationship with histopathological subtype has recently been shown on primary tumor but has not been evaluated on metastases. The aim of our work is to analyze PD-L1 expression within each histopathological pattern on resected metastases. Material and Methods: 136 patients were included in this retrospective study. Immunohistochemistry was performed with 22C3 laboratory-developed test. The Tumor Proportion Score was evaluated on each subtype. Results: The most frequent major histopathological subtype was solid (n = 69, 50.7 %), followed by acinar (n = 37, 27.2 %), micropapillary (n = 14, 10.3 %) and papillary (n = 10, 7.3 %). Mean percentage of PD-L1 expression for each subtype was at 28+/-4.8 % for solid subtype, 5.3+/-1.9 % for acinar subtype, 5+/-1.9 % for papillary subtype and 23.6+/-4.1 % for micropapillary subtype. Mean percentage of PD-L1 expression was different between solid pattern and acinar pattern (p < 0.001), solid pattern and papillary pattern (p = 0.007), micropapillary pattern and acinar pattern (p < 0.001) and micropapillary pattern and papillary pattern (p = 0.015).Conclusion: To conclude, we have showed firstly that several patterns are present in metastases of lung adenocarcinoma, secondly that the evaluation of patterns and PD-L1 stain on different patterns is reproducible, thirdly that pattern heterogeneity is related to PD-L1 staining, fourthly that in metastatic lung adenocarcinoma with at least two patterns, solid and micropapillary subtypes have higher levels of PD-L staining, fifthly that PD-L1 heterogeneity between different patterns is not a rare event. These results might explain discrepancies of PD-L1 results between biopsies and surgical samples and the fact that some patients might respond to checkpoint inhibitors even though PD-L1 expression is low or absent.