542P - Down-regulation of γ-glutamyl hydrolase gene expression in tumor tissues is associated with response to oral uracil and tegafur/leucovorin chemothe...
|Date||01 October 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation III|
|Topics|| Colon Cancer
S. Sadahiro1, T. Suzuki1, A. Tanaka1, K. Okada1, A. Kamijo1, H. Nagase2, J. Uchida2
5-Flurouracil (5-FU)/leucovorin (LV) and oral uracil and tegafur (UFT)/LV are widely used as standard adjuvant chemotherapy for colorectal cancer (CRC). We previously reported that right-sided tumors with high thymidine phosphorylase (TP) gene expression on pre-chemotherapy tumor biopsy are associated with a response to UFT/LV chemotherapy in patients with CRC. In the present study, we examined the relation between chemotherapy-induced gene expression changes (post-chemotherapy/pre-chemotherapy gene expression ratio) in CRC tissues and the efficacy of UFT/LV treatment.Material and methods
The subjects were 73 patients with CRC who were scheduled to undergo surgery. UFT (300 mg/m2/day) and LV (75 mg/day) were administered for 2 weeks before surgery. We assessed pathological response based on the extent of residual cancer cells and granulation tissue. The mRNA expressions of 6 pyrimidine-related enzymes and 8 reduced folate-related enzymes were quantitatively evaluated using a RT-PCR assay in paired samples of pre-chemotherapy tumor-biopsy specimens and post-chemotherapy resected-tumor specimens.Results
Pathological responses were observed in 19.2% (14/73) of the patients. Gene expression of γ-glutamyl hydrolase (GGH) was generally down-regulated after chemotherapy, and the extent of GGH down-regulation among the responders was significantly greater than that among the non-responders, with the least p value of 0.0009 among the genes studied. The extent of GGH down-regulation among right-sided tumors with high sensitivity to UFT/LV chemotherapy was significantly greater than that among left-sided tumors (p = 0.0135). Moreover, on combined analysis of tumor site and sex, the extent of GGH down-regulation among left-sided tumors in men that showed low sensitivity to UFT/LV chemotherapy was significantly smaller than that among other tumors (p = 0.0018).Conclusion
Down-regulation of GGH gene expression in primary CRC tissues after UFT/LV chemotherapy is associated with a response to chemotherapy in patients with CRC.Disclosure
H. Nagase: He is an employee of Taiho Pharmaceutical Co.
J. Uchida: He is an employee of Taiho Pharmaceutical Co.
All other authors have declared no conflicts of interest.