Ezrin–Radixin–Moesin Binding Phosphoprotein 50: A Potential Novel Biomarker in Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinomas

• Published in: Head & neck pathology (Totowa, N.J.) Vol. 13; no. 2; pp. 188 - 197
• Main Authors: Shankar, Athiva, Crouch, Dorothy H., Macluskey, Michaelina
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2019
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Dentistry; Female; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Oral and Maxillofacial Surgery; Original Paper; Otorhinolaryngology; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; Pathology; Phosphoproteins - analysis; Phosphoproteins - biosynthesis; Retrospective Studies; Sodium-Hydrogen Exchangers - analysis; Sodium-Hydrogen Exchangers - biosynthesis; Squamous Cell Carcinoma of Head and Neck - diagnosis; Squamous Cell Carcinoma of Head and Neck - virology; Oropharyngeal cancers; Head and neck squamous cell carcinoma; Human papilloma virus; EBP50
• ISSN: 1936-0568; 1936-055X; 1936-0568
• DOI: 10.1007/s12105-018-0937-z

High-risk human papilloma virus (HR-HPV) has increasingly been associated with head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal cancers. Ezrin–Radixin–Moesin Binding Phosphoprotein 50 (EBP50), a putative tumour suppressor, localises to the plasma membrane in suprabasal epithelium and to the cytoplasm in proliferative basal layers, and is a target for degradation by the HR-HPV E6 oncoprotein. The aim of this study was to investigate EBP50 protein expression patterns in HNSCC in a large Scottish cohort to determine if there was a correlation with HPV status and clinical outcomes. EBP50 expression patterns were assessed in 156 HNSCC including oropharyngeal (37.8%), laryngeal (24%), oral (19%) and other sites (18.5%), which were genotyped for presence of HR-HPV. HNSCC were generally negative for membranous EBP50. EBP50 expression was either cytoplasmic/absent, being ‘predominantly cytoplasmic’ in 76 (49%), ‘weak/negligible cytoplasmic’ in 44 (28%), ‘strongly cytoplasmic’ in 5 (3%), ‘heterogeneous’ in 26 (17%) and ‘other’ in 5 (3%) samples. Forty tumours (25%) were positive for HPV DNA, predominantly HR-HPV 16, and 44 (28%) were p16 positive. The majority of tumours (71%) with ‘weak/negligible cytoplasmic’ EBP50 expression originated in the oropharynx were more likely to have positive neck nodes, overexpression of p16 and positive tumour HR-HPV status ( P  < 0.001). Differences in EBP50 levels between oropharyngeal and non-oropharyngeal tumours may be linked to degradation of EBP50 by HR-HPV, and loss of EBP50 may therefore be a surrogate biomarker for HR-HPV infection in oropharyngeal tumours.