The methylation status and expression of human telomerase reverse transcriptase is significantly high in oral carcinogenesis

APMIS. 2017 Sep;125(9):797-807. doi: 10.1111/apm.12723. Epub 2017 Aug 2.

Abstract

Telomerase activity is present in most cancers and is tightly regulated by the expression of human telomerase reverse transcriptase (hTERT). Hypermethylation in the promoter region of hTERT contributes to the regulation of hTERT expression. In this study, we investigated the methylation and expression of hTERT in oral squamous cell carcinoma (OSCC), oral leukoplakia, and normal oral mucosa. Furthermore, we investigated the significance of hTERT to the clinicopathological findings of OSCC. 35 OSCC, 50 oral leukoplakia (epithelial dysplasia n = 25, squamous cell hyperplasia n = 25), and 10 normal oral mucosa samples were investigated through methylation-specific PCR. Immunohistochemistry was analyzed in 35 OSCC, 50 oral leukoplakia, and 4 normal oral mucosa samples. The methylation and expression of hTERT increased from normal oral mucosa to oral leukoplakia to OSCC. In OSCC, all samples were methylated. However, partial methylation (20%) or unmethylation (80%), but never complete methylation, was observed in normal oral mucosa. Additionally, hTERT expression correlated with cervical lymph node metastasis. These results suggested that the methylation and expression of hTERT is high in oral carcinogenesis and may play an important role in oral cancer. hTERT expression may also be predictive of cervical lymph node metastasis.

Keywords: DNA methylation; Human telomerase reverse transcriptase; oral leukoplakia; oral squamous cell carcinoma; telomerase.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • DNA Methylation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen / biosynthesis
  • Leukoplakia, Oral / genetics*
  • Leukoplakia, Oral / pathology
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism*
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / biosynthesis*
  • Telomerase / genetics*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • TERT protein, human
  • Telomerase