Intratumor heterogeneity (ITH) detection remains a challenge in modern oncology because it can have a direct impact on the success of new therapies. Anti-PD-1/PD-L1 immunotherapy is an emerging treatment modality that is showing great promise for clear cell renal cell carcinoma (CCRCC) patients with advanced disease. Patient selection for such therapy relies upon the immunohistochemical detection of PD-1/PD-L1, however the degree of ITH for these markers among tumor cells and/or inflammatory mononuclear infiltrates remains unknown. Therefore, we analyzed PD-L1 (SP-142) expression in the tumor inflammatory cells of 22 CCRCC cases with the aim to define the pattern of PD-L1 expression, and to compare the reliability of current tumor sampling protocols (RS) with a multisite tumor sampling strategy (MSTS). While the RS protocol identified 5/22 (22.7%) of cases that were positive for PD-L1 expression, MSTS identified 10/22 (45.45%) of cases. This suggests that RS may miss a proportion of CCRCC patients that might benefit from immunotherapy. In addition, MSTS demonstrated that positive and negative regions of PD-L1 expression are very variable within each tumor.
Pathology, research and practice. 2018 Jun 12 [Epub ahead of print]
José I López, Rafael Pulido, Jesús M Cortés, Javier C Angulo, Charles H Lawrie
Department of Pathology, Cruces University Hospital, Barakaldo, Spain; Biomarkers in Cancer Unit, Biocruces Research Institute, Barakaldo, Spain; Department of Medical-Surgical Specialties, University of the Basque Country (UPV/EHU), Leioa, Spain. Electronic address: ., Biomarkers in Cancer Unit, Biocruces Research Institute, Barakaldo, Spain; IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain., IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain; Quantitative Biomedicine Unit, Biocruces Research Institute, Barakaldo, Spain; Department of Cell Biology and Histology, University of the Basque Country (UPV/EHU), Leioa, Spain., Department of Urology, University Hospital of Getafe, Getafe, Madrid, Spain; Clinical Department, European University of Madrid, Laureate Universities, Madrid, Spain., IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain; Molecular Oncology, Biodonostia Research Institute, Donostia-San Sebastián, Spain; Department of Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain; Radcliffe Department of Medicine, University of Oxford, UK.