Combined CD44, c‐MET, and EGFR expression in p16‐positive and p16‐negative head and neck squamous cell carcinomas

Purpose/Objective(s) To examine the association between CD44 and c‐MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC). Materials/Methods Immunohistochemical staining of CD44, p16, EGFR, and c‐MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c‐MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease‐free survival (DFS) and overall survival (OS). Results High CD44 expression was present in 33% of patients and was associated with non‐oropharynx primaries (P < 0.001), high c‐MET expression (P < 0.001), p16‐negative (P < 0.001) and EGFR‐positive tumors (P < 0.001). Fifty‐seven percent of CD44 high expressing tumors had high c‐MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16–5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46–4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30–4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c‐MET expression had a poor prognosis with a 2‐year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T‐stage, smoking history, and EGFR status, high c‐MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43). Conclusions High CD44 expression is associated with high c‐MET expression, p16‐negative tumors, and EGFR‐positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation.