Clinical significance of expression of thymidylate synthase and dihydropyrimidine dehydrogenase in oral squamous cell carcinoma

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  • Tsuzuki Masako
    Department of Oral and Maxillofacial Surgery, Tokyo Medical University
  • Satomi Takafumi
    Department of Oral and Maxillofacial Surgery, Tokyo Medical University
  • Chiba Hiroshige
    Department of Oral and Maxillofacial Surgery, Tokyo Medical University

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Abstract

To evaluate the molecular mechanism underlying the antitumor effect of the 5-fluorouracil (5-FU) family on oral cancers, we examined immunohistochemical profiles for thymidylate synthase (TS), a target of 5-FU, and its catabolizing enzyme, dihydropyrimidine dehydrogenase (DPD) in oral squamous cell carcinomas (SCCs). In addition, we investigated whether TS and DPD might be capable of serving as predictors of the anticancer efficacy of the 5-FU family or as prognostic factors. Immunohistochemistry for TS and DPD was performed on formalin-fixed paraffin sections of initial biopsy specimens from 53 patients with primary oral squamous cell carcinoma who received neoadjuvant chemotherapy with 5-FU and with S-1, an improved equivalent of 5-FU, and we also investigated 16 surgical samples of recurrent or metastatic SCC cases. When immunopositive areas for TS and DPD in five unit fields were determined respectively as their expression ratios, TS expressions in stage III-IV tumors were significantly higher than those in stage I-II tumors. The TS expressions in recurrent/metastatic tumors tended to be higher than those of tumors with no recurrence. Tumors with lower TS and DPD expressions had higher responses to 5-FU (P=0.006). We also found correlations between the TS and DPD expression rates and the response levels to 5-FU. The results indicate that the TS and DPD expressions are capable of serving as predictors of the efficacy of these anticancer agents as well as prognostic factors for oral SCCs.

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