Thymidylate synthase and dihydropyrimidine dehydrogenase expression in oral squamous cell carcinoma: an immunohistochemical and clinicopathologic study.
OBJECTIVE
Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU), and dihydropyrimidine dehydrogenase (DPD) is the first enzyme that metabolizes 5-fluorouracil. Until now, only the enzyme activities of TS and DPD have been investigated; however, there are few reports about the immunohistochemistry of TS and DPD and none regarding oral carcinoma. The purpose of this article was to investigate the expression of TS and DPD in oral squamous cell carcinoma.


METHODS
In this study, 109 oral squamous cell carcinomas were investigated for the immunohistochemical expression of TS and DPD proteins.


RESULTS
The expressions of TS in carcinoma cases was significantly higher than in controls (P <.05, t test). DPD was expressed both in carcinomas and in areas adjacent to the carcinomas. There was no correlation between the clinical factors and the TS labeling index or between the clinical factors and the DPD labeling index (DPD-LI). Pathologically, DPD-LI was significantly different in both the World Health Organization classification and Anneroth's classification. The TS labeling index was significantly correlated with the Ki-67 LI (P <.05, Pearson's correlation coefficient). Although TS showed no correlation between tegafur-uracil response and TS labeling index, there was a significant correlation between the tegafur-uracil response and DPD-LI.


CONCLUSIONS
TS may reveal tumor cell proliferation, but DPD-LI may correlate with a response to anticancer drug treatment.
Kawasaki
Goro
G
Division of Oral and Maxillofacial Surgery, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan. gkawa@net.nagasaki-u.ac.jp
Yoshitomi
Izumi
I
Yanamoto
Souichi
S
Mizuno
Akio
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009367:Neoplasm Staging; D010088:Oxidoreductases / Q000096:biosynthesis*; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D014498:Uracil / Q000008:administration & dosage
D019394:Ki-67 Antigen; D005641:Tegafur; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase