Abstract
As a nuclear and nucleolar protein, proliferation marker protein Ki-67 (Ki-67) serves a vital role in tumorigenesis due to its positive correlation with tumor proliferation. High expression of Ki-67 in the cell cycle from the G1 to M phase makes it a potential biomarker for certain tumors and useful for selecting medical treatment. However, the diagnostic value of Ki-67 in oral squamous cell carcinoma (OSCC) has not been fully evaluated. In the present study, the objective was the elucidation of the prognostic value of Ki-67 in a large number of OSCC patients. Ki-67 expression was detected by immunohistochemical staining methods in 298 OSCC specimens and 98 tumor-free oral mucosa specimens (62 dysplasia mucosa and 36 normal mucosa), acquired from Nanjing Stomatological Hospital, Medical School of Nanjing University (Nanjing, China). Expression of Ki-67 in normal tissues, dysplasia tissues and OSCC tissues was compared. Associations between Ki-67 expression and clinicopathological parameters were analyzed by χ2 test. Kaplan-Meier survival curves and Cox progression analysis were used to assess the diagnostic value of Ki-67 for OSCC. The results showed that Ki-67 expression was higher in OSCC tissues than in tumor-free tissues and that it increased with the progression of dysplasia in oral mucosa tissues. In addition, patients with high Ki-67 expression had a worse clinical outcome, including poor tumor differentiation (P=0.001), increased positive lymph node metastasis (P=0.006) and increased worst pattern of invasion type (P<0.0001). Kaplan-Meier survival analysis demonstrated that higher Ki-67 expression was associated with poorer overall survival (OS) (P=0.035), recurrence-free survival (RFS) (P=0.017), metastasis-free survival (MFS) (P=0.032) and disease-free survival (DFS) (P=0.018) times. Additional multivariate analysis demonstrated that Ki-67 expression was negatively associated with OS, DFS, RFS and MFS. In conclusion, Ki-67 overexpression is associated with the progression of OSCC and serves as an independent prognostic factor for OSCC patients.