title: What is the Prognostic Significance of Ki-67 Positivity in Oral Squamous Cell Carcinoma?
abstract: BACKGROUND
  Numerous studies have stated that Ki-67 is a good prognostic marker in oral squamous cell carcinoma (OSCC). However, some researchers believe the contrary. To address this controversy, we performed a systematic literature retrieval to estimate the prognostic significance of Ki-67 expression in patients with OSCC.
  
  
  METHODS
  Databases covering Pubmed, Ovid, Web of Science, Embase and the Cochrane library were searched regardless of publication year. Overall survival (OS), local recurrence (LR) and disease-free survival (DFS) were the main outcome measures. Relative risks (RRs) and its 95% confidential intervals (CIs) were used for statistical analysis.
  
  
  RESULTS
  Twenty-seven articles with 2146 patients were included in this study. The results of the meta-analysis suggested that the pooled RRs and its CIs for OS, LR, and DFS were 1.45 (1.15 - 1.84), 1.76 (0.74 - 4.16) and 1.52 (1.07 - 2.14), respectively. However, the heterogeneities of OS and LR were obvious (I-squared (OS) = 59.4%, I-squared (LR) = 72.6%). After subgroup analysis based on systemic treatment, the cut-off value of Ki-67 expression, ethnicity and types of antibody, the heterogeneities became acceptable. It was observed that systemic treatment, cut-off values of Ki-67 expression, ethnicity and the types of antibody affected the results. The statistical analyses of subgroups suggested that non-systemic treatment, (OR=1.77, 95% CI = 1.39-2.25, p = 0.000) and Asian populations (OR=2.09, 95% CI = 1.32-3.32, p = 0.002) are high risks for Ki-67 high expression, and low cut-off value of Ki-67 expression (OR = 1.44, 95% CI = 1.001-2.072), MIB-1 antibody (OR = 1.48, OR 95% = 1.10-1.99) might affect the identification of results.
  
  
  CONCLUSIONS
  According to this meta-analysis, high Ki-67 expression might be a negative prognostic marker of patients with OSCC, especially in Asian populations. In addition, Ki-67 expression affects the treatment response.
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;
authors.forename: Shang
authors.initials: S
authors.lastname: Xie
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2. Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100191, China;
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.affiliation: 3. Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Rui-Xi
authors.initials: RX
authors.lastname: Hua
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Shan
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China;
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Cai
keywords: Ki-67; Meta-analysis.; OSCC; Oral squamous cell carcinoma; Prognosis; Survival