p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival

Eur Arch Otorhinolaryngol. 2014 Jun;271(6):1641-51. doi: 10.1007/s00405-013-2833-1. Epub 2014 Jan 9.


To examine the prognostic significance of the immunohistochemical expression of p63 and Ki-67 oncoproteins in patients with laryngeal squamous cell carcinoma, a retrospective evaluation was carried out on a cohort of 108 patients with primary laryngeal squamous cell carcinoma (LSCC) treated by primary surgery. For the immunohistochemical evaluation, tissue section obtained by formalin-fixed and paraffin-embedded tissue blocks from resection of each patient was used. Clinicopathologic data were associated with the immunostaining results. The association among the considered variables was assessed by Fisher's exact test, Mann-Whitney test, non-parametric χ(2) test, and Spearman's rho rank test was used to assess the relations among them. Differences in p63 and Ki-67 immunoreactivity among the different groups were compared via Kruskal-Wallis test and post hoc tests were performed using Mann-Whitney test with Bonferroni correction. The overall survival rate was estimated via Kaplan-Meier method, and the cumulative incidence functions for different groups were compared using log-rank statistics. Cox proportional hazard model was employed in a multivariate analysis to assess the effect of prognostic factors in the overall survival rate. Furthermore, taking into account death due to other causes, we estimated LSCC-related survival and disease-free survival rates using competing risk analysis. The results of immunohistochemical examination showed a statistically significant relationship between the up-regulation of P63 and Ki-67, an increase in histological grading, and primary tumours associated with lymph node metastases. p63 and Ki-67 up-regulation was related to a shorter disease-free survival and a significant association was found between p63 and Ki-67 percentage of positive cells and patient survival. Finally, we noticed a significant relation between p63 and Ki-67 (ρ = 0.87). On the other hand, no statistically significant associations were found between p63 and Ki-67 down-regulation and clinicopathologic data. Our findings suggest that abnormal p63 and Ki-67 immunoreactivity may be involved in the early phases of laryngeal tumorigenesis and may become a significant prognostic predictor for both overall and disease-free survivals. These biomarkers could thus help in the selection of high-risk patients with LSCC who may benefit from more aggressive therapy or chemoprevention.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / surgery
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Laryngeal Neoplasms / surgery
  • Laryngectomy
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck
  • Up-Regulation


  • CKAP4 protein, human
  • Ki-67 Antigen
  • Membrane Proteins