title: Notch1 Overexpression Correlates to Improved Survival in Cancer of the Oropharynx.
abstract: Objectives The Notch1 signaling pathway has recently been shown to be highly dysregulated in head and neck squamous cell carcinoma, but the value of Notch1 as a predictive biomarker is yet to be elucidated in oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to evaluate Notch1 expression in surgical OPSCC specimens and determine clinicopathologic correlates. Study Design Case series with planned data collection. Setting Tertiary academic medical center. Subjects and Methods Surgical specimens from 181 patients with OPSCC were collected to create a tissue microarray (TMA). Human papillomavirus (HPV) status and Notch1 expression were determined and correlated with clinicopathologic characteristics. Results In univariate analysis, Notch1 expression correlated with improved survival as a categorical variable (hazard ratio [HR], 0.346; P < .0001) and correlated with HPV/p16 positivity as a continuous variable ( P < .0001). In multivariate analysis, Notch1 expression retained significance in HPV-positive (HR, 0.303; P = .033) and HPV-negative (HR, 0.416; P = .0055) subgroups. Similarly, Notch1 expression positively correlated with survival in p16-positive (HR, 0.469; P = .031) and p16-negative subgroups (HR, 0.310; P = .014). Conclusions In the largest OPSCC cohort to date, we found that Notch1 receptor expression positively correlates with overall survival, regardless of HPV or p16 status. Furthermore, we found higher Notch1 receptor expression in HPV/p16-positive tumors than their HPV/p16-negative counterparts.
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Azeem S
authors.initials: AS
authors.lastname: Kaka
authors.affiliation: 2 Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Nowacki
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.affiliation: 3 Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors.forename: Songzhu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Old
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Enver
authors.initials: E
authors.lastname: Ozer
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Carrau
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Schuller
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 1 Department of Otolaryngology, Division of Head and Neck Surgery and The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D053208:Kaplan-Meier Estimate; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D027383:Papillomaviridae / Q000302:isolation & purification; D011379:Prognosis; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
keywords: Notch1 expression; human papillomavirus; oropharyngeal squamous cell carcinoma