Ki67 Overexpression in mucosa distant from oral carcinoma: A poor prognostic factor in patients with long-term follow-up

J Craniomaxillofac Surg. 2016 Sep;44(9):1430-5. doi: 10.1016/j.jcms.2016.06.011. Epub 2016 Jun 21.


Purpose: The aggressive behavior of oral squamous cell carcinoma (OSCC) has recently been related to the mucosa surrounding the primary mass, consisting of genetically altered cells that might be responsible for cancer progression. The aim of the study was to determine whether an abnormal cell turnover in clinically and histologically "normal" mucosa distant from the primary tumor is associated with a poor prognosis in terms of locoregional control (LRC) of disease and disease-specific survival (DSS).

Material and methods: This prospective study monitored 55 OSCC patients. Cell turnover in areas clinically and histologically distant from the tumor mass was evaluated by immunohistochemical expression of Ki67. A Ki67 value >20% was considered "high."

Results: The mean follow-up period of the population studied was 53.7 ± 32.4 months (range 12-110 months). Multivariate analysis showed that the Ki67 value in distant mucosa was a powerful independent prognostic factor for LRC. In addition, high Ki67 expression in distant mucosa was the only variable statistically related to worse LRC (χ(2) = 9.5; p = 0.002) and DSS (χ(2) = 5.51; p = 0.02) in T1-2N0 OSCCs.

Conclusions: The present study confirmed the role of Ki67 in tumor-distant areas as a prognostic marker for OSCC patients.

Keywords: Distant mucosa; Field cancerization; Immunohistochemistry; Ki67; Oral squamous cell carcinoma; Prognosis.

MeSH terms

  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / surgery
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies


  • Ki-67 Antigen