title: Histopathological response to preoperative chemotherapy including 5-fluorouracil additionally assessed by immunocytochemical and pharmacologic parameters in patients with advanced gastric cancer.
abstract: To investigate quantitative methods for assessing the response to preoperative downstaging chemotherapy (PDC), the immunocytochemical expression of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) as well as a pharmacologic study of the rate of thymidylate synthetase inhibition (TSIR) were studied in resected specimens obtained from patients with advanced gastric cancer. Fifty-one patients with advanced gastric cancer who received PDC (30 with 5-fluorouracil peroral administration and the other 21 with intravenous administration of 5-fluorouracil and cisplatin) were studied. The labeling index of PCNA (PCNA-LI) and BrdU were measured. The PCNA suppression (PCNA-S), which was measured by both the values of prechemotherapeutic PCNA-LI in endoscopically biopsied specimens and postchemotherapeutic PCNA-LI in resected specimens, was also examined. TSIR was measured by a protein-bound radiochemical method. We compared the above-mentioned parameters with the histopathological response to PDC according to the General Rules for Gastric Cancer Study. In the patients with peroral 5-flurorouracil, a stepwise regression analysis showed that TSIR is a significantly effective for determining the histopathological response to PDC. In the patients with 5-fluorouracil and cisplatin, PCNA-S was the most effective indicator of the histopathological response to PDC, as shown by a stepwise regression analysis. The present study thus showed that both TSIR and PCNA-S were effective additional indicators of the histopathological response to PDC.
authors.affiliation: Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Namatame
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Kumada
mesh_terms: D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001973:Bromodeoxyuridine / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005468:Fluorodeoxyuridylate / Q000494:pharmacology*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D011300:Preoperative Care; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014316:Tritium
chemical_list: D000964:Antimetabolites, Antineoplastic; D018809:Proliferating Cell Nuclear Antigen; D014316:Tritium; D005468:Fluorodeoxyuridylate; D013940:Thymidylate Synthase; D001973:Bromodeoxyuridine; D002945:Cisplatin; D005472:Fluorouracil