Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma

Oral Dis. 2017 May;23(4):505-510. doi: 10.1111/odi.12641. Epub 2017 Mar 9.

Abstract

Background: Acetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers.

Objective: To investigate HDAC1, HDAC2 and HAT1 expression in lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) and to demonstrate their correlation with DNA metyltransferases (DNMTs).

Material and methods: Thirty cases of lip squamous cell carcinoma (LSCC), thirty cases of actinic cheilitis (AC), and 28 cases of non-neoplastic epithelium as control were selected for immunohistochemical investigation.

Results: Nuclear HDAC2 immunopositivity was significantly higher in AC (75.07% ± 29.70) when compared with LSCC (51.06% ± 39.02). HDAC1 and HAT1 nuclear immunostaining were higher in AC, with no statistical significance. When comparing data with our previous study, we found a positive correlation between HDAC1 X DNMT1/DNMT3b, HDAC2 X DNMT3b, and HAT1 X DNMT1/DNMT3b for certain studied groups.

Conclusion: This study showed higher levels of nuclear HDAC2 immunopositivity in AC, possibly indicating that this enzyme plays a key role in lip photocarcinogenesis early stages.

Keywords: actinic cheilitis; histone acetyltransferases; histone deacetylases; immunohistochemistry; lip neoplasms; squamous cell carcinoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / enzymology*
  • Case-Control Studies
  • Cheilitis / enzymology*
  • Child
  • Child, Preschool
  • DNA Modification Methylases / metabolism
  • Female
  • Histone Acetyltransferases / metabolism*
  • Histone Deacetylase 1 / metabolism*
  • Histone Deacetylase 2 / metabolism*
  • Humans
  • Immunohistochemistry
  • Lip Neoplasms / enzymology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA Modification Methylases
  • Histone Acetyltransferases
  • histone acetyltransferase type B complex
  • HDAC1 protein, human
  • HDAC2 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2

Supplementary concepts

  • Actinic cheilitis