Fabien Forest1, François Casteillo2, Vanessa Da Cruz3, Violaine Yvorel4, Tiphanie Picot5, François Vassal6, Olivier Tiffet7, Michel Péoc'h2. 1. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Pathology, Avenue Albert Raimond, 42055 Saint Etienne, France; University Hospital of Saint Etienne, North Hospital, Molecular Biology of Solid Tumours Unit, Avenue Albert Raimond, 42055 Saint Etienne, France; Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Neurosurgery, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. Electronic address: f.forest@univ-st-etienne.fr. 2. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Pathology, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. 3. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Pathology, Avenue Albert Raimond, 42055 Saint Etienne, France; Hospices Civils de Lyon, Institut de Pathologie Multisite, Groupement Hospitalier Sud, Department of Pathology, Pierre-Bénite, France; Centre Hospitalier de Bourg-en-Bresse, Department of Pathology, 900, route de Paris, CS 90401, 01012 Bourg En Bresse, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. 4. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Pathology, Avenue Albert Raimond, 42055 Saint Etienne, France; University Hospital of Saint Etienne, North Hospital, Molecular Biology of Solid Tumours Unit, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. 5. University Hospital of Saint Etienne, North Hospital, Molecular Biology of Solid Tumours Unit, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. 6. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Neurosurgery, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France. 7. Centre Hospitalier Universitaire de Saint Etienne, Hôpital Nord, Department of Thoracic Surgery, Avenue Albert Raimond, 42055 Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France.
Abstract
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.
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.
Authors: Alice Court; David Laville; Sami Dagher; Vincent Grosjean; Pierre Dal-Col; Violaine Yvorel; François Casteillo; Sophie Bayle-Bleuez; Jean-Michel Vergnon; Fabien Forest Journal: Diagnostics (Basel) Date: 2022-06-29