title: CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity.
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.
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Straub
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Enken
authors.initials: E
authors.lastname: Drecoll
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pfarr
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.|National Center of Tumor Diseases (NCT), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Institute of Medical Statistics and Epidemiology, Technical University of Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hapfelmeier
authors.affiliation: Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Götz
authors.affiliation: Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Klaus-Dietrich
authors.initials: KD
authors.lastname: Wolff
authors.affiliation: Department of Oral and Maxillofacial Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kolk
authors.affiliation: Institute of Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Specht
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: PD-1; PD-L1; Pathology Section; fluorescence in situ hybridization; gene amplification; oral squamous cell carcinoma