Research ArticlesThe Loss of p16 Expression Worsens the Prognosis of OSCCPérez-Sayáns, Mario PhD, DDS*; Suárez-Peñaranda, José M. MD, PhD†; Padín-Iruegas, Marí E. MD, PhD‡; Gayoso-Diz, Pilar MD*,§; Reis-De Almeida, Miguel DDS*; Barros-Angueira, Francisco PhD∥; Gándara-Vila, Pilar MD, DDS, PhD*; Blanco-Carrión, Andrés MD, PhD*; García-García, Abel MD, PhD*Author Information *Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS) †Department of Pathology and Forensic Sciences, University Hospital and School of Medicine of Santiago de Compostela ‡Laboratorio Oncología Traslacional, Fundación Idichus §Clinical Epidemiology and Biostatistics Unit, Hospital Clínico Universitario de Santiago de Compostela ∥Unidad de Medicina Molecular—Fundación Pública Galega de Medicina Xenómica. Edificio de Consultas planta-2, Hospital Clínico Universitario, Santiago de Compostela, Spain The authors declare no conflict of interest. Reprints: Mario Pérez-Sayáns, PhD, DDS, Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS), Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain (e-mail: [email protected]). Received January 14, 2014 Accepted July 15, 2014 Applied Immunohistochemistry & Molecular Morphology: November/December 2015 - Volume 23 - Issue 10 - p 724-732 doi: 10.1097/PAI.0000000000000133 Buy Metrics Abstract Oral squamous cell carcinoma is the most common neoplasia of the mouth. Downregulation of p16INK4a (a cyclin-dependent kinase inhibitor) has been reported for mouth cancer and it is believed that its inactivation is an early event in oral carcinogenesis. The goal of this article is to quantitatively report expression of p16INK4a and the state of methylation in oral squamous cell carcinoma, and evaluate its relationship with the clinical and prognostic factors, in addition to setting out a multivariate model that predicts survival. The mean expression of p16INK4a was 7.70 (SD=14.07) (F=0.894; P=0.449). According to the semiquantitative analysis, there were statistically significant differences, where 19 cases were negative (<2 %), 11 at initial stages, and 8 at advanced stages (χ2=6.016; P<0.05). The methylation of p16INK4a was not associated with any of the clinical or pathologic variables. Kaplan-Meier curve showed a better survival for patients in initial stages (40.72 mo) compared to those in advanced stages (28.6 mo) (P<0.01). Survival was also reduced in a statistically significant manner in patients with any degree of dysplasia in the adjacent margin (P<0.05). During univariate Cox regression analysis, it was observed that individuals with relapse had a higher risk (almost 9 times higher) [P<0.001; hazard ratio=8.91; 95% confidence interval (CI), 4.18-19.02]. During the Cox multivariate analysis for each unit of decrease in p16INK4a, the risk increased by 1.06) (P<0.05; hazard ratio=0.94; 95% CI, 0.89-1.00). p16INK4a expression is reduced with advancing tumor stage and its gene silencing is associated with an increased risk of death. Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.