Association between expression of folate-metabolizing and 5-FU target enzymes and effects of chemotherapy in colorectal cancer

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Reproducible detection of folate metabolism-related proteins in routine and pathological samples presented difficulties. However, immunostaining was useful for analyzing expression of pyrimidine-synthesizing enzymes and cell death markers. High expression of thymidine kinase-1 and thymidylate synthase was detected prominently in gastrointestinal and uterine carcinomas. Spontaneous levels of cleaved (active) caspase-9 (CC9) correlated with antitumor effect of S-1, an oral fluoropyrimidine. Gastric carcinomas outnumbered in CC9-positive tumors while colorectal carcinomas in LC3-positive tumors.