Do the expression of CD44, apoptosis and thymidylate synthase inhibition rate correlate with the efficacy of chemotherapy in colorectal cancer?

Background: Tegafur-uracil(UFT; TAIHO Pharmaceutical Co.Ltd, Tokyo, Japan) is commonly used to treat digestive cancers. However, the inhibitors of met astasis in this agent have not been fully examined. To investigate a cell a dhesion molecule, CD44, which may very well contribute to the pathogenesis of metastasis, we examined the association of CD44 and the thymidylate synt hase inhibition rate(TSIR) with prognosis, and examined the expression of a poptosis in patients who were administrated tegafur-uracil before surgery f or colorectal cancer: Mataials and Methods: This study included 66 patients who underwent curative resection of colorectal cancer. in these patients, tegafur-uracil(600mg) was orally administered elmy day for 3 to 7 days befo re surgery, and Tegafur-uracil (400mg) was orally administered every day fo r 2 years after surgery. CD44 and apoptosis were defected immunohistochemic ally and by the TUNEL method respectively. The TSIR was calculated from the total TS level, and fr ee TS levels by modified Spears' method using fresh tumor tissue specimens. Results: The TSIR of non-recurrent patients was si gnificantly higer than that of recurrent patients(p<0.05). The 5-year survi val I ate in CD44-low grade positive/negative patients (81.6%) was signific antly higher than that in CD44-high grade positive patients (46.4%) (p<0.00 5). The 5-year survival rate in apoptosis-high grade positive patients(89.7 %) was significantly higher than that in apoptosis-low grade positive/negat ive patients(46.4%) (p<0.001). With respect to the relationship between CD4 4 and apoptosis, the proportion Of apoptosis-high grade positive patients a mong CD44-low grade positive/negative patients (55.3%) was significantly hi gher than that among CD44-high grade positive patients(28.6%) (p<0.05). In the multivariate analysis, the CD44 expression was suggestive of an indepen dent prognostic factor. Conclusion: Based on our results for TSIR, Tegafur- uracil may induce apoptosis of tumor cells in patients by the inhibition of thymidylate synthase. It was suggested that CD44 expression could be used as a possible independent predictor of survival. In addition, it was sugges ted that UFT, via the inhibition of CD44 expression caused the inhibition o f distant metastasis.