Date Published: March 27, 2018
Author(s): Luís Silva Monteiro, Márcio Diniz-Freitas, Saman Warnakulasuriya, Tomás Garcia-Caballero, Jerónimo Forteza-Vila, Máximo Fraga.
We analysed the expression of cyclins A2, B1, D1, and E1 by immunohistochemistry and numerical aberrations in CCND1 gene by fluorescence in situ hybridization technique in 67 primary oral squamous cell carcinomas (OSCC). Cyclin A2 expression was observed in 54 (83.1%) tumours, cyclin D1 in 58 (89.2%), cyclin B1 in 39 (60%), and cyclin E in 21 (32.8%). CCND1 region analysis revealed 26 (43.3%) tumours with the presence of numerical aberrations which were correlated with cyclin D1 high expression (Rho = 0.48; p < 0.001). Twenty-nine (45.3%) tumours were classified as high proliferative tumours assessed by Ki-67 protein expression and correlated with tumours with high expression of cyclin A2 (Rho = 0.30; p = 0.016) and cyclin B1 (Rho = 0.37; p = 0.003). In multivariate analysis for an overall five-year survival (OS), we found an adverse independent prognostic value for cyclin A2 high expression (p = 0.031) and for advanced tumour stage (p < 0.001). Our results confirm that several cyclins are commonly expressed in OSCC. CCND1 gene is abnormal in more than one-third of the cases and is frequently associated with cyclin D1 high expression. Moreover, cyclin A2 high expression is an independent indicator of worse OS suggesting that this protein may serve as a reliable biological marker to identify high-risk subgroups with poor prognosis.
Oral cancer remains a significant cause of morbidity and mortality, with 529,451 new cases and 292,289 estimated deaths annually worldwide in 2012 . Over 90 percent of cancers of the oral cavity are represented by oral squamous cell carcinomas (OSCC). Despite technological advances in the detection and management of oral cancer during the last few decades, many centres still report low survival rates (~50%) .
Deregulation and aberrations of cell cycle-related cyclins have been implicated in the tumour growth and progression of several cancers [3, 5]. The understanding of these alterations in tumorigenesis may identify new proteins that may serve as important cancer diagnostic and prognostic indicators as well as potential targets for therapeutic approaches in patients with OSCC [16, 23]. With this in mind, we conducted this study to evaluate the influence of the expression of the cyclins A2, B1, D1, and E1 and CCND1 gene status on clinical, pathologic, and prognostic characteristics of patients with OSCC.