P14 methylation: an epigenetic signature of salivary gland mucoepidermoid carcinoma in the Serbian population

Oral Surg Oral Med Oral Pathol Oral Radiol. 2018 Jan;125(1):52-58. doi: 10.1016/j.oooo.2017.09.013. Epub 2017 Sep 28.


Objective: To investigate the prevalence of p16INK4 a, p14ARF, tumor protein p53 (TP53), and human telomerase reverse transcriptase (hTERT) promoter hypermethylation in mucoepidermoid carcinomas (MECs) and search for a possible association between methylation status and clinicopathological parameters.

Study design: DNA extracted from 35 formalin-fixed and paraffin-embedded MEC samples and 10 normal salivary gland (NSG) tissue samples was analyzed for the presence of promoter hypermethylation using methylation-specific polymerase chain reaction testing.

Results: The percentages of gene hypermethylation in MECs versus NSGs were the following: p14: 100% versus 20% (P<.001); p16: 60% versus 20% (P = .035); hTERT: 54.3% versus 20% (P = .078); and TP53: 31.4% versus 30% (P = .981). Multiple sites were found to be methylated in 86% of MECs compared with 10% in NSGs (P< .001). TP53 and hTERT were more often methylated in lower clinical stages (P = .033 and P = .005, respectively).

Conclusions: Hypermethylation of p14 appears to be an important event in the development of mucoepidermoid carcinoma. High frequency of gene hypermethylation and high incidence of methylation at multiple sites point to the importance of epigenetic phenomena in the pathogenesis of MECs, although with modest impact on clinical parameters.

MeSH terms

  • Carcinoma, Mucoepidermoid / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation / genetics*
  • Epigenomics
  • Female
  • Genes, p53 / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Salivary Gland Neoplasms / genetics*
  • Serbia
  • Telomerase / genetics
  • Tumor Suppressor Protein p14ARF / genetics*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Protein p14ARF
  • Telomerase