Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma

•NOTCH1 was frequently expressed in head and neck squamous cell carcinomas (HNSCC).•NOTCH1 expression correlated with HES1 and p21 expression.•NOTCH1/HES1/p21 positive cases had a significantly better prognosis.•Our results suggest a tumor suppressor function for NOTCH signaling in HNSCC. The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis. Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients. Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P