Klin Onkol 2002; 15(2): 72-75.
Summary: 5-fluorouracil and related fluoropyrimidine drugs are often used for the treatment of gastrointestinal cancers. Unfortunatelly tumors of some patients are resistant to these drugs. The chemoresistance is associated with changes in the level of expression of genes coding enzymes for pyrimidine metabolism in tumor cells. These genes can be used as predictors of chemoresistance to fluoropyrimidine anti-cancer drugs. This study shows the difference between the levels of transcription of genes for two key enzymes of pyrimidine metabolism in samples from different parts of colorectal tumors. The transcription levels of thymidylate synthase /TS/ gene are often increased in tumor cells, compared to reference nontumorous tissue. Median for TS mRNA is 1.55 in cancer tissue compared to 0.9 for control mucosa under identical experimental conditions. The transcription levels of dihydropyrimidine dehydrogenase /DPD/ are moderately lowered in tumor tissue compared to reference nontumorous tissue. The difference in numerical value of TS mRNA levels between different parts of the same tumor can vary by more than 60% under identical conditions of determination. Metastases have usually different mRNA levels of TS and DPD than the primary tumor tissues. Thus, for the objective results, at least two samples should be collected from every tumor. Moreover, it is recommended to take samples from metastases if possible.
