Ki-67 from clinically and histologically "normal" distant mucosa as prognostic marker in early-stage (T1-T2N0) oral squamous cell carcinoma: a prospective study

J Oral Maxillofac Surg. 2011 Oct;69(10):2579-84. doi: 10.1016/j.joms.2010.10.041. Epub 2011 Feb 3.


Purpose: The aggressive behavior and long-term prognosis of oral squamous cell carcinoma (OSCC) have recently been related to the mucosa surrounding the primary mass, consisting of genetically altered cells that might be responsible for cancer progression. Early-stage T1-T2N0 OSCCs have been associated with a good prognosis; however, a certain percentage of them can be complicated by locoregional metastases. The purpose of our study was to determine whether an abnormal proliferative status can be found in clinically and histologically "normal" mucosa situated in areas distant from the primary tumor. We also sought to determine whether this is associated with a poor prognosis in terms of local recurrence or lymph node metastasis.

Patients and methods: The prospective study included 42 consecutive patients with T1N0M0 (n = 19) and T2N0M0 (n = 23) OSCC. Disease-free survival endpoints were defined as the duration between surgical resection and the diagnosis of recurrence, lymph node metastasis, or last follow-up visit. Proliferative status in distant areas (opposite cheek) was evaluated by Ki-67 expression.

Results: The mean Ki-67 value (17.6% ± 8.2%) in the distant mucosa was significantly greater (F = 13.87; P < .01) than that found in the controls (9.8 ± 3.1). "Abnormally high" Ki-67 values were detected in 13 patients with OSCC (30%). Four patients developed locoregional recurrence during follow-up. Kaplan-Meier analysis showed that Ki-67 in the distant mucosa was a significant independent prognostic factor for disease-free survival.

Conclusions: A certain percentage of patients surgically treated for early T1-T2 OSCC will have an abnormal proliferative status in areas very distant from the primary tumor that seems to be related to a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Case-Control Studies
  • Cell Proliferation
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis*
  • Ki-67 Antigen / biosynthesis
  • Linear Models
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Mucosa / chemistry*
  • Mouth Mucosa / metabolism
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / surgery
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies


  • Biomarkers, Tumor
  • Ki-67 Antigen