BACKGROUND
Although heregulin and HER3 are frequently expressed at high levels in head and neck cancer, their prognostic value remains unclear. We explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well as p16 status.
METHODS
Ninety-six primary tumor specimens from OPSCC patients were retrospectively collected and analyzed for heregulin mRNA by in situ hybridization and for HER3, EGFR, and HER2 by quantitative immunohistochemistry. Heregulin and HER3 mRNA levels were also examined among different tumor types using The Cancer Genome Atlas (TCGA) database.
RESULTS
High heregulin mRNA (> median) correlated significantly with poor OS (HR: 8.48; 95% CI: 2.17–33.17; P = 0.002) but not DFS (HR: 1.52; 95% CI: 0.64–3.65; P = 0.344), in OPSCC patients. Heregulin mRNA correlated negatively with OS in both p16-positive (P = 0.049) and p16-negative (P = 0.091) OPSCC patients on univariate analysis. High HER3 (> median) also correlated with poor OS (HR: 4.68; 95%CI: 1.47–14.90; P = 0.009) on multivariate analysis. EGFR levels independently correlated with DFS (P = 0.025) and inversely correlate with p16 status (P = 0.012). In addition, TCGA data showed that head and neck squamous cell carcinoma exhibits higher heregulin expression compared to other solid tumor types examined. CONCLUSION: High heregulin mRNA and high HER3 protein levels independently correlate with poor OS in OPSCC. These data support targeting HER3 in heregulin-high OPSCC and warrant further clinical investigation.