title: The Loss of p16 Expression Worsens the Prognosis of OSCC.
abstract: Oral squamous cell carcinoma is the most common neoplasia of the mouth. Downregulation of p16(INK4a) (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 p16(INK4a) 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 p16(INK4a) 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 (χ(2)=6.016; P<0.05). The methylation of p16(INK4a) 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 p16(INK4a), the risk increased by 1.06) (P<0.05; hazard ratio=0.94; 95% CI, 0.89-1.00). p16(INK4a) expression is reduced with advancing tumor stage and its gene silencing is associated with an increased risk of death.
authors.affiliation: *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.
authors.forename: Mario
authors.initials: M
authors.lastname: Pérez-Sayáns
authors.forename: José M
authors.initials: JM
authors.lastname: Suárez-Peñaranda
authors.forename: Marí E
authors.initials: ME
authors.lastname: Padín-Iruegas
authors.forename: Pilar
authors.initials: P
authors.lastname: Gayoso-Diz
authors.forename: Miguel
authors.initials: M
authors.lastname: Reis-De Almeida
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros-Angueira
authors.forename: Pilar
authors.initials: P
authors.lastname: Gándara-Vila
authors.forename: Andrés
authors.initials: A
authors.lastname: Blanco-Carrión
authors.forename: Abel
authors.initials: A
authors.lastname: García-García
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm