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Original Investigation
March 4, 2017

Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities

Author Affiliations
  • 1Department of Dermatology, Stanford University School of Medicine, Redwood City, California
  • 2Dermatopathology Service, Department of Pathology, Stanford University School of Medicine, Redwood City, California
JAMA Dermatol. Published online March 4, 2017. doi:10.1001/jamadermatol.2016.5062
Key Points

Question  What is the expression of programmed death ligand 1 (PD-L1) in basal cell carcinomas (BCCs) given that PD-L1 expression has been associated with response to programed death 1 inhibitor immunotherapy in other tumor types?

Findings  In this cross-sectional study of 138 BCCs from 62 patients, 89.9% were positive for PD-L1 immunohistochemical staining in tumor cells, and 94.9% were positive for PD-L1 expression in tumor-infiltrating lymphocytes. In a multivariable model, PD-L1 expression of treated BCCs was significantly increased in tumor cells and tumor-infiltrating lymphocytes compared with treatment-naive BCCs.

Meaning  The high rate of PD-L1 positivity in BCCs and tumor-infiltrating lymphocytes suggests that programmed death 1 inhibitor immunotherapy may have activity against BCCs.

Abstract

Importance  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.

Objective  To assess PD-L1 expression in treatment-naive and treated BCCs.

Design, Setting, and Participants  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.

Exposures  Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.

Main Outcomes and Measures  Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.

Results  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).

Conclusions and Relevance  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.

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