ATM, THMS, and RRM1 protein expression in nasopharyngeal carcinomas treated with curative intent

Head Neck. 2016 Apr:38 Suppl 1:E384-91. doi: 10.1002/hed.24004. Epub 2015 Jun 29.

Abstract

Background: In advanced nasopharyngeal carcinoma (NPC), biomarkers may help predict survival.

Methods: Tumoral expression of ataxia-telangiectasia mutated (ATM), thymidylate synthetase (THMS), and ribonucleotide reductase subunit M1 (RRM1), was correlated with survival in patients with nonmetastatic NPC using quantitative fluorescence immunohistochemistry with automated quantitative digital image analysis.

Results: Of the 146 patients included, 58 patients (40%) received concurrent chemoradiation therapy; the remainder was treated with radiation. Overall survival (OS) at 5 years was 71% (95% confidence interval [CI], 62% to 78%); disease-free survival (DFS) was 48% (95% CI, 39% to 57%). OS worsened for increasing values of ATM (hazard ratio [HR], 2.83; 95% CI, 1.01-7.94; p = .049) for values greater than the 75th percentile compared to less than the 25th percentile, but improved for tumors with higher THMS levels (HR, 0.44; 95% CI, 0.20-0.94; p = .033) for values greater than the 25th percentile compared to less than or equal to the 25th percentile. RRM1 was not associated with OS (p = .748). No biomarkers were associated with DFS.

Conclusion: In our cohort, relative overexpression of ATM and low THMS levels were associated with worse OS. © 2015 Wiley Periodicals, Inc. Head Neck 38: E384-E391, 2016.

Keywords: ataxia-telangiectasia mutated (ATM); nasopharyngeal carcinoma; ribonucleotide reductase subunit M1 (RRM1); thymidylate synthetase (THMS).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Biomarkers, Tumor / metabolism
  • Carcinoma / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism*
  • Ribonucleoside Diphosphate Reductase
  • Survival Rate
  • Thymidylate Synthase / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Thymidylate Synthase
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins