title: Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities.
abstract: Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.
  
  
  
  To assess PD-L1 expression in treatment-naive and treated BCCs.
  
  
  
  This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.
  
  
  
  Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.
  
  
  
  Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.
  
  
  
  Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P = .003) and TILs (47% vs 18%, P = .008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P = .007).
  
  
  
  Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Julia
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Gefei A
authors.initials: GA
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Christine
authors.initials: C
authors.lastname: Cheung
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California2Dermatopathology Service, Department of Pathology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Redwood City, California.
authors.forename: Anne Lynn S
authors.initials: AL
authors.lastname: Chang
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000473:pathology* / Q000628:therapy; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000473:pathology* / Q000628:therapy
chemical_list: D060890:B7-H1 Antigen