Journal des biomarqueurs moléculaires et du diagnostic

Prognostic Value of Cell Cycle Proteins in Squamous Cell Carcinomas of the Oral Cavity

Abstract

Marcilei Eliza Cavicchioli Buim, José Humberto Fregnani, Silvia Vanessa Lourenço, Cibele Pidorodeski Nagano, André Lopes Carvalho and Fernando Augusto Soares

The cell cycle is under strict regulation. Cyclin-dependent kinases (CDKs) at the G1-S and G2-M checkpoints are positively regulated by cyclins and negatively regulated by CDK inhibitors. Oral squamous cell carcinoma (OSCC) is a common malignancy that is characterized by a high degree of local aggression and lymph node metastasis. We examined positive regulators of the cell cycle (cyclin A, cyclin B1, and cyclin D1), cell cycle inhibitors (p16, p21, p27, p53, and Rb), and the proliferation markers Ki-67 and topoisomerase IIA by immunohistochemistry in a tissue microarray, comprising 136 cases of OSCC. Expression of cyclin A, cyclin B1, cyclin D1, topoisomerase IIA, p53, and Rb was positively associated with Ki-67. Overexpression of cyclin D1 correlated with the presence of lymph node metastasis. Overexpression of cyclin A, cyclin D1, topoisomerase IIA, and Rb and downregulation of p21 and p27 were associated with reduced overall survival in OSCC patients. Cyclin A, p21 and p27, were implicated an independent prognostic factor, by multivariate analysis, in OSCC patients. In conclusion, cyclin A, cyclin D1, p21 and p27 expression can be a valuable marker of poor prognosis and tumor aggressiveness in OSCC.