Measurement of intratumoral expression of
dihydropyrimidine dehydrogenase (DPD) and thymidylate
synthase (TS) may have some value in predicting the
response to fluoropyrimidine-containing therapy. Patients
and Methods: We attempted to validate this association
in a series of Russian metastatic colorectal cancer
cases. While replicating already published protocols, we
unexpectedly found that the use of commonly utilized
gene referees, glyceraldehyde-3-phosphate dehydrogenase
(GAPDH) and beta-actin, may lead to artifacts due
to pseudogene-driven amplification from the genomic
DNA template. We have developed a real-time PCR protocol
which amplifies short PCR fragments, thus allowing
efficient analysis of archival formalin-fixed paraffin-embedded
tumor samples, and relies on succinate dehydrogenase
(SDHA) as a gene referee, therefore avoiding amplification
from genomic DNA. Results: Low content of
DPD transcripts was observed in 13/20 (65%) patients
with disease control (tumor response or disease stabilization)
as compared to only 3/9 (33%) subjects with progressive
disease (p = 0.11). Despite the low number of
patients, this association reached the level of statistical
significance when similar analysis was done for TS expression
(11/20 (55%) vs. 1/9 (11%); p = 0.03). Conclusions:
Our data confirm that low DPD and TS expressors
have higher chances of success of fluoropyrimidine-containing
regimens.