title: A quantitative evaluation of the determinant proteins for S-1 responsiveness in a biopsy specimen assists in patient selection to neoadjuvant therapy in cases of advanced gastric cancer.
abstract: Neoadjuvant chemotherapy (NAC) by 5-fluorouracil including S-1 is administered to advanced gastric cancer patients. However, the therapeutic benefit from this pre-operative treatment remains uncertain. The present study analyzed the expression of 5-fluorouracil related enzymes, TS, DPD and OPRT in 47 gastric cancer biopsy specimens using quantitative double-fluorescence immunohistochemistry (qDFIHC), which is a newly developed system to quantify protein expression. The study first determined whether the cancer heterogeneity within the sample influences evaluation by qDFIHC system. Thereafter, the expression values of the TS, DPD, OPRT and OPRT/TS, OPRT/DPD, OPRT/(TS+DPD) ratios were retrospectively correlated with the clinical or pathological response in the patients. The expression values of TS, DPD and OPRT at a single field were significantly correlated with mean of the values evaluated at three fields. Among the 6 candidate factors analyzed, OPRT, OPRT/TS, OPRT/DPD and OPRT/(TS+DPD) showed significant correlations with the clinical response in 47 patients. Cut-off values to differentiate the clinical response were determined in the four factors. OPRT/TS showed the strongest correlation with the clinical response. qDFIHC was able to quantify the TS, DPD and OPRT expressions in cancer biopsy specimens without being affected by the heterogeneity. Effective therapy using tailored S-1 NAC according to the OPRT/TS ratio is therefore expected in advanced gastric cancer patients.
authors.affiliation: Department of Surgery, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Keita
authors.initials: K
authors.lastname: Kai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hiraki
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Tokunaga
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Noshiro
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010094:Oxonic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D013048:Specimen Handling; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005641:Tegafur / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil