Prognostic value of Ki67 from clinically and histologically 'normal' distant mucosa in patients surgically treated for oral squamous cell carcinoma: a prospective study

Int J Oral Maxillofac Surg. 2009 Nov;38(11):1165-72. doi: 10.1016/j.ijom.2009.06.011. Epub 2009 Jul 16.


The frequent spread of oral squamous cell carcinoma (OSCC) has been explained by the persistence of genetically altered mucosa after surgery. This study examined whether clinically and histologically 'normal' mucosa distant from the primary tumour (from the opposite cheek) has an abnormal proliferative status, and whether this is associated with poor prognosis in terms of local recurrence or lymph node metastasis. The prospective study included 47 consecutive patients with OSCC. Disease-free survival endpoints were defined as the duration between surgical resection and the diagnosis of recurrence, lymph node metastasis, death or last follow-up. Proliferative status was evaluated by Ki67 expression. The mean Ki67 value (16.5+/-8.9) in the distant mucosa was statistically higher than that in controls (8.8+/-2.9). Abnormally high Ki67 values (>20%) were detected in 11 OSCC patients (23%). Multivariate analysis showed that Ki67 value in distant mucosa was a powerful independent prognostic factor, greater than tumour differentiation or clinical stage for the disease-free survival rate; it was statistically negative regarding local recurrence. Some patients surgically treated for OSCC have an abnormal proliferative status in areas distant from the primary tumour. The Ki67 value in these areas is a promising prognostic factor.

MeSH terms

  • Aged
  • Analysis of Variance
  • Biomarkers, Tumor* / analysis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cell Proliferation
  • Disease-Free Survival
  • Female
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / biosynthesis*
  • Linear Models
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / surgery
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies


  • Biomarkers, Tumor
  • Ki-67 Antigen