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Histopathological response to preoperative chemotherapy including 5-fluorouracil additionally assessed by immunocytochemical and pharmacologic parameters in patients with advanced gastric cancer.
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.