DNA replication licensing factor MCM2, geminin, and Ki67 define proliferative state and are linked with survival in oral squamous cell carcinoma.

Abstract

Oral squamous cell carcinoma (OSCC) is still an unabated global killer with little advancement in its survival rate. DNA replication licensing proteins and Aurora kinase A are biomarkers that play important roles in genomic stability. The expression profile of minichromosomal maintenance protein 2 (MCM2), Ki67, geminin, and Aurora-A were linked to clinicopathological and outcome parameters, survival, and DNA content in 125 cases of OSCC. Oral fibroepithelial polyps (OFEP) were controls. The OSCC tumour cells were in a rapidly proliferating state, as assessed by the increased expression profile of MCM2, Ki67, geminin, and Aurora-A and of the geminin/Ki67 ratio, and the decrease of the MCM2/Ki67 ratio, in OSCC compared with OFEP (P<0.000). There was an association between expression of MCM2, Ki67, and geminin and tumour histologic and invasive front grade (P<0.05). A total of 82% of the OSCC assessed had aneuploid DNA content, which was associated with increased expression intensity of Aurora-A (P=0.01). Geminin and the geminin/Ki67 ratio were associated with TNM staging (P<0.05), and weak expression of MCM2, Ki67, geminin, and Aurora-A were predictive of OSCC survival (P<0.05). Dysregulation of the origin licensing pathway and the mitotic pathway are important events in OSCC, and the combined analysis of these proteins may contribute to improved treatment decisions.