Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase expression in tumor tissue, regarding the efficacy of postoperatively administered UFT (tegafur+uracil) in patients with non-small cell lung cancer.
BACKGROUND
UFT (tegafur + uracil) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined.


METHODS
Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection, and had been administered UFT post-surgery. The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining. The relationship between TS and/or DPD expression and clinicopathological factors was examined.


RESULTS
There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative and 32 DPD-positive cases. There was no significant difference between the patients with TS or DPD and those without TS or DPD in age, gender, histological type or p-stage. The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%, respectively (p<0.001). The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5%, while 10-year survival rates were 22.7 and 95.5%, respectively (p<0.001). There was no significant difference between DPD-positive and DPD-negative patients in prognosis.


CONCLUSIONS
The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low. Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC.
Miyoshi
Takanori
T
Department of Oncological and Regenerative Surgery, Institute of Health Bioscience, University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
Kondo
Kazuya
K
Toba
Hiroaki
H
Yoshida
Mitsuteru
M
Fujino
Haruhiko
H
Kenzaki
Koichiro
K
Sakiyama
Shoji
S
Takehisa
Masatsugu
M
Tangoku
Akira
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase