<i>CD274/PD-L1</i>gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

Abstract

// Melanie Straub 1 , Enken Drecoll 1 , Nicole Pfarr 1 , Wilko Weichert 1,5,6 , Rupert Langer 2 , Alexander Hapfelmeier 3 , Carolin G&ouml;tz 4 , Klaus-Dietrich Wolff 4 , Andreas Kolk 4 and Katja Specht 1 1 Institute of Pathology, Technical University of Munich, Munich, Germany 2 Institute of Pathology, University of Bern, Bern, Switzerland 3 Institute of Medical Statistics and Epidemiology, Technical University of Munich, Munich, Germany 4 Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany 5 National Center of Tumor Diseases (NCT), Heidelberg, Germany 6 German Cancer Consortium (DKTK), Heidelberg, Germany Correspondence to: Katja Specht, email: // Keywords : PD-L1, PD-1, oral squamous cell carcinoma, fluorescence in situ hybridization, gene amplification, Pathology Section Received : January 22, 2016 Accepted : January 30, 2016 Published : February 22, 2016 Abstract Immunomodulatory therapies, targeting the immune checkpoint receptor-ligand complex PD-1/PD-L1 have shown promising results in early phase clinical trials in solid malignancies, including carcinomas of the head and neck. In this context, PD-L1 protein expression has been proposed as a potentially valuable predictive marker. In the present study, expression of PD-L1 and PD-1 was evaluated by immunohistochemistry in 80 patients with predominantly HPV-negative oral squamous cell carcinomas and associated nodal metastasis. In addition, CD274/PD-L1 gene copy number status was assessed by fluorescence in situ hybridization analysis. PD-L1 expression was detected in 36/80 (45%) cases and concordance of PD-L1 expression in primary tumor and corresponding nodal metastasis was present in only 20/28 (72%) cases. PD-1 expression was found in tumor-infiltrating lymphocytes (TILs) but not in tumor cells. CD274/PD-L1 gene amplification was detected in 19% of cases, with high level PD-L1 amplification present in 12/80 (15%), and low level amplification in 3/80 (4%). Interestingly, CD274/PD-L1 gene amplification was associated with positive PD-L1 immunostaining in only 73% of cases. PD-L1 copy number status was concordant in primary tumor and associated metastases. Clinically, PD-L1 tumor immunopositivity was associated with a higher risk for nodal metastasis at diagnosis, overall tumor related death und recurrence. Based on our findings we propose to include PD-L1 copy number status in addition to protein status in screening programs for future clinical trials with immunotherapeutic strategies targeting the PD-1/PD-L1 axis.