Dihydropyrimidine dehydrogenase expression predicts survival outcome and chemosensitivity to 5-fluorouracil in patients with oral squamous cell carcinoma.
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (5-Fu) catabolism. The aim of this study was to evaluate the prognostic value of DPD expression and the correlation between DPD expression and efficacy of 5-Fu. Retrospective analysis of DPD expression was performed immunohistochemically in 103 patients with oral squamous cell carcinoma (OSCC), in which staining intensity of DPD expression and degree of heterogeneity of DPD expression were categorized. Expression of DPD correlated with lymph node metastasis, mode of invasion and differentiation. Expression of DPD was an independent significant factor for survival outcome and was more predictive than conventional clinical factors. Furthermore, heterogeneous expression of DPD was more effective than homogeneous expression of DPD in neoplastic cells when evaluated in patients treated with chemotherapy including tegafur/uracil (UFT). Expression of DPD is an independent predictor for clinical outcome. Furthermore, heterogeneity of DPD expression may be a clue for predicting sensitivity to 5-Fu in patients with OSCC.
Kobayashi
Hiroichi
H
Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan. h-koba@hsp.md.shinshu-u.ac.jp
Koike
Takeshi
T
Nakatsuka
Atsushi
A
Kurita
Hiroshi
H
Sagara
Junji
J
Taniguchi
Shun'ichiro
S
Kurashina
Kenji
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil