Thymidylate synthase and dihydropyrimidine dehydrogenase are related to histological effects of 5-fluorouracil and cisplatin neoadjuvant chemotherapy for primary gastric cancer patients.
Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and vascular endothelial growth factor (VEGF) are associated with the effect of 5-fluorouracil (5-FU) based adjuvant chemotherapy. However, very few studies have investigated the relationship between these factors and 5-FU neoadjuvant chemotherapy for primary gastric cancer patients. In this study, we studied the correlation between these markers and the histological chemotherapeutic effect in advanced gastric cancer with neoadjuvant chemotherapy.


METHODS
Sixty-two primary advanced gastric cancer patients were recruited into the study. One cycle of continuous infusion of 5-FU (300 mg/m2/day, 14 days) plus drip infusion of cisplatin (15 mg/m2/day, Day one and Day two) was performed as neoadjuvant chemotherapy. Histological chemotherapeutic responses of the resected specimens were classified into responders and nonresponders. TS, DPD, VEGF expressions both before and after neoadjuvant chemotherapy were examined immunohistochemically.


RESULTS
There was an association between the TS-low group and the responders (p < 0.05); the DPD-low group and the responders in both biopsy and surgical specimens (p < 0.01). A combination of the low-TS and low-DPD group was further associated with responders (p < 0.01). The immunoexpressions of biopsied and surgical specimens were significantly associated with each other.


CONCLUSIONS
Neoadjuvant chemotherapy for primary gastric cancer with one cycle of 5-FU and cisplatin was associated with histological findings in patients with low baseline TS and DPD. This dual determination may predict for efficacy of neoadjuvant treatment with these drugs.
Fukuda
Hiroyuki
H
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takiguchi
Nobuhiro
N
Koda
Kenji
K
Oda
Kenji
K
Seike
Kazuhiro
K
Miyazaki
Masaru
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002945:Cisplatin / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil