Measurement of DPD and TS transcripts aimed to predict clinical benefit from fluoropyrimidines: confirmation of the trend in Russian colorectal cancer series and caution regarding the gene referees.
BACKGROUND
Measurement of intratumoral expression of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) may have some value in predicting the response to fluoropyrimidine-containing therapy.


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.
Iyevleva
Aglaya G
AG
N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
Buslov
Konstantin G
KG
Togo
Alexandr V
AV
Matsko
Dmitry E
DE
Filimonenko
Vasily P
VP
Moiseyenko
Vladimir M
VM
Imyanitov
Evgeny N
EN
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016477:Artifacts; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D012426:Russia; D013385:Succinate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D012334:RNA, Neoplasm; D042943:Dihydrouracil Dehydrogenase (NADP); D013385:Succinate Dehydrogenase; D013940:Thymidylate Synthase; D005472:Fluorouracil