p16INK4A in oral squamous cell carcinomas--a correlation with biological behaviors: immunohistochemical and FISH analysis

J Oral Maxillofac Surg. 2006 Nov;64(11):1617-23. doi: 10.1016/j.joms.2005.11.097.

Abstract

Purpose: The p16(INK4A) gene and Rb gene are key tumor suppressor genes in a cell cycle regulatory pathway that is commonly inactivated in various cancers. The disruption of p16(INK4A) expression has been reported in several types of carcinoma but sparse in the area of oral oncology.

Materials and methods: The study included 66 cases who were diagnosed as oral squamous cell carcinoma. Immunohistochemical p16(INK4A) and pRb expression, fluorescence in situ hybridization analysis were performed to the resected materials.

Results: p16(INK4A) protein expressions were detected in 14 cases without lymph node metastasis versus in 4 cases with metastasis (P = .04). As to histopathological grading of the effect of chemotherapy, almost all the p16(INK4A)-positive cases (9 cases out of 10) exhibited the histological feature of being rather sensitive to chemotherapy (2B and better response according to Ohboshi and Shimosato's criteria) versus 17 of 33 negative cases (P = .02). Survival curves showed that the survival rate of patients with loss of p16(INK4A) expression was significantly worse than those with amplification and normal genetic dosage of p16(INK4A) (P < .0001).

Conclusions: The expressions of p16(INK4A) were significantly correlated with biological behavior of OSCCs. These results indicate we can use p16(INK4A) as a marker of a prognostic prediction of oral cancer and it is useful for management of OSCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Chi-Square Distribution
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / chemistry*
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / genetics
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Retinoblastoma Protein / analysis
  • Retinoblastoma Protein / genetics
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein