Predictive Role of Dihydropyrimidine Dehydrogenase (DPD) and Thymidylate Synthase (TS) Gene Expressions in Patients with Metastatic Colorectal Cancer Treated with Capecitabine
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- Category: Vol. 77, June 2009
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Predictive Role of Dihydropyrimidine Dehydrogenase (DPD) and Thymidylate Synthase (TS) Gene Expressions in Patients with Metastatic Colorectal Cancer Treated with Capecitabine, MOHAMAD ABD EL-KADER, MAGDA ALAM, MOHAMAD MAZROH, MAMDOUH EL-SHERBINY,
NADER MOHAMED and AMAL F. GHARIB
Abstract
Background and Objective: Dihydropyrimidine dehydro-genase (DPD) and thymidylate synthase (TS) gene expressions in metastatic colorectal cancer have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. In present study, we investigated the association between both DPD and TS expressions in metastatic colorectal cancer and the response and survival in patients treated with capecitabine.
Patients and Methods: DPD and TS expressions were measured by reverse transcription-PCR in tissues obtained by ultrasound-guided needle biopsy from 37 patients who went on to receive oral treatment of capecitabine for metastatic colorectal cancer. Relative mRNA amounts of DPD or TS were expressed as the ratios of targeted gene to glyceraldehyde-3-phosphate dehydrogenase reverse transcription-PCR prod-ucts.
Results: Median values of DPD mRNA expressions were 0.30 and 0.65 for responding tumors and nonresponding ones, respectively, with a statistical significance (p<0.0001). No responding tumor had a DPD mRNA expression >!0.5. A total of 19 tumors had low DPD mRNA expressions of <0.5, and 63% of them showed response. There was no responding tumor with both high DPD and high TS (TS mRNA expression 1.0). However, the response rate was 75% in tumors with both low DPD and low TS. The median survival time was 16.3 months in patients with both low DPD and low TS versus 8.4 months in patients with high DPD or high TS mRNA expression.
Conclusion: In conclusion, the combination of DPD and TS mRNA expressions in metastatic tumor might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.