Research Papers: Pathology:
CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 3442 views | HTML 4592 views | ?
Abstract
Melanie Straub1, Enken Drecoll1, Nicole Pfarr1, Wilko Weichert1,5,6, Rupert Langer2, Alexander Hapfelmeier3, Carolin Götz4, Klaus-Dietrich Wolff4, Andreas Kolk4 and Katja Specht1
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.
![Creative Commons License](/images/80x15.png)
PII: 7593