Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma

Sung Wei Lee, Tzu Ju Chen, Li Ching Lin, Chien Feng Li, Li Tzong Chen, Chung-Hsi Hsing, Han Ping Hsu, Chia Jung Tsai, Hsuan Ying Huang, Yow Ling Shiue

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC). In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR. Immunoexpression of TYMS and DHFR were retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high TYMS (50%) expressions were correlated with primary tumor (p=0.008) and AJCC stage (p=0.006), and high DHFR (50%) expression were correlated with nodal status (p=0.039) and AJCC stage (p=0.029) (7th American Joint Committee on Cancer), respectively. In multivariate analyses, high TYMS expression emerged as an independent prognosticator for worse disease-specific survival (p<0.001), distal metastasis-free survival (p=0.002) and local recurrence-free survival (p<0.001), along with AJCC stage. Therefore, TYMS expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through dysregulation of the nucleotide biosynthetic process.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalExperimental and Molecular Pathology
Issue number1
Publication statusPublished - Aug 2013
Externally publishedYes


  • Nasopharyngeal carcinoma
  • Survival
  • TYMS
  • Thymidylate synthetase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry


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