ATM in oral carcinogenesis: association with clinicopathological features

J Cancer Res Clin Oncol. 2008 Sep;134(9):1013-20. doi: 10.1007/s00432-008-0365-7. Epub 2008 Feb 21.

Abstract

Purpose: The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response. Our aim here was to investigate the expression profile and loss of heterozygosity (LOH) of ATM, as well as their relationships to clinicopathological parameters in oral premalignant lesions (leukoplakia) and primary oral squamous cell carcinoma (OSCC).

Methods: Immunohistochemical assay and PCR were performed to detect the expression profile and LOH at D11S2179 of ATM. The association between clinicopathological parameters and the changes of ATM was statistically analyzed.

Results: ATM protein levels were higher in oral leukoplakia than those in normal controls, while the expressions of ATM protein had a versatile tendency in OSCC: 10 samples (31.25%) showed increased ATM protein levels than those observed in normal tissues, 12 samples (37.50%) had the same protein levels as the normal tissues, and 10 samples (31.25%) showed reduced or absent ATM levels. The patients with reduced/absent ATM expression had more poorly-differentiated situation as well as the tendency for lymph node metastasis. Most interestingly, 50% of these reduced cases were younger than 50 years old. PCR for LOH assay displayed that none of the samples from oral leukoplakia had abnormal changes in D11S2179, while three samples (9.38%) of OSCC showed loss of heterozygosity, and two samples (6.25%) with microsatellite instability.

Conclusions: These findings suggest that overexpression of ATM may be one of the early events in the carcinogenesis of OSCC. ATM might be a candidate biomarker for diagnosis and prognosis in OSCC, as well as a possible genetic marker for early-onset OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia Mutated Proteins
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Leukoplakia, Oral / genetics
  • Leukoplakia, Oral / pathology*
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases