Histone Modification Patterns Correlate With Patient Outcome in Oral Squamous Cell Carcinoma

Cancer. 2013 Dec 15;119(24):4259-67. doi: 10.1002/cncr.28356. Epub 2013 Sep 24.


Background: Patterns of global histone modifications have been suggested to be predictors of clinical outcome in many cancers. However, the role of global histone modification patterns in oral squamous cell carcinoma (OSCC) is unclear.

Methods: A retrospective clinicopathologic analysis was undertaken of 186 patients with oral squamous cell carcinoma who received complete ablative surgical treatment. Tissue arrays were made from those paraffin-embedded OSCC samples and examined by immunohistochemistry for histone 3 lysine 4 acetylation (H3K4ac), histone 3 lysine 18 acetylation (H3K18ac), histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and histone 3 lysine 27 trimethylation (H3K27me3).

Results: A low level of H3K4ac and a high level of H3K27me3 were associated with advanced T status, N status, tumor stage, and perineural invasion. They were also correlated with cancer-specific survival (CSS) and disease-free survival (DFS). The 5-year CSS and DFS in H3K4ac(low) vs. H3K4ac(high) were 74.8% versus 92.5% (P = .010), and 51.4% versus 76.2% (P = .001), respectively. The 5-year CSS and DFS in H3K27me3(low) versus H3K27me3(high) were 94.7% versus 62.3% (P < .001) and 76.4% versus 32.3% (P < .001), respectively. We also found improved prediction for DFS after combining the H3K4ac(low) and H3K27me3(high) profiles and comparing the scores with the other modification patterns (P < .0001).

Conclusions: This research demonstrates the potential prognostic utility of global histone modification analysis for OSCC.

Keywords: histone modification; oral squamous cell carcinoma; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / surgery
  • Histones / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / surgery
  • Prognosis
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck


  • Biomarkers, Tumor
  • Histones