A Correlative Analysis of PD-L1, PD-1, PD-L2, EGFR, HER2, and HER3 Expression in Oropharyngeal Squamous Cell Carcinoma

• Authors: Conor Steuer, Emory University; Christopher Griffith, Emory University; Sreenivas Nannapaneni, Emory University; Mihir Patel, Emory University; Yuan Liu, Emory University; Kelly Magliocca, Emory University; Mark El-Deiry, Emory University; Cynthia Cohen, Emory University; Taofeek Owonikoko, Emory University; Dong Shin, Emory University; Georgia Chen, Emory University; Nabil Saba, Emory University
• Journal Title: Molecular Cancer Therapeutics
• Volume: Volume 17, Number 3
• Publisher: American Association for Cancer Research | 2018-03-01, Pages 710-716
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1535-7163.MCT-17-0504
• Subjects: Health Sciences, Oncology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; TUMOR-INFILTRATING LYMPHOCYTES; HPV-ASSOCIATED HEAD; NECK-CANCER; PLUS CETUXIMAB; LUNG-CANCER; IMMUNITY; NIVOLUMAB; SAFETY; CHEMORADIOTHERAPY; CHEMOTHERAPY

Abstract

We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by IHC on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0 to 4 within the tumor mass and peritumoral stroma. Associations between biomarkers and patient outcomes were tested using descriptive and inferential statistics, logistic regression, and Cox proportional hazards models. We analyzed tissue samples from 97 OPSCC cases: median age 59 years, p16þ (71%), male (83.5%), never smokers (18%), stage 3 to 4 disease (77%). Twenty-five percent of cases were PD-L1 positive. The proportion of PD-L1þ tumors was higher in p16þ (29%) than p16 OPSCC (11%, P ¼ 0.047). There was no correlation between PD-L1, PD-L2, PD-1, EGFR, HER2, or HER3 expression. Positive PD-L1 status correlated with advanced nodal disease on multivariate analysis (OR 5.53; 95% CI, 1.06–28.77; P ¼ 0.042). Negative PD-L2 expression was associated with worse survival (HR 3.99; 95% CI, 1.37–11.58; P ¼ 0.011) in p16 OPSCC. Lower density of PD-1 positive lymphocytes in peritumoral stroma was associated with significantly increased risk of death on multivariate analysis (HR 3.17; 95% CI, 1.03–9.78; P ¼ 0.045) after controlling for prognostic factors such as stage and p16 status. PD-L1 expression on tumor cells correlates with p16 status and advanced nodal status in OPSCC. PD-1 positive lymphocytes in peritumoral stroma serve as an independent prognostic factor for overall survival.