Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients.
BACKGROUND
The predictive value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression on long-term survival by influencing 5-fluorouracil (5-FU) effect were determined in primary tumours and node metastases of stage III colon cancer patients treated adjuvantly with 5-FU regimens (n=391). The effect of TP 53 mutation status, which is thought to be functionally linked to TS inhibition, was also examined.


METHODS
TS and DPD protein expression was determined by immunohistochemical analysis using tissue microarrays of these colon tumours. Two hundred and twenty tumours had already been screened in a previous study for TP 53 mutations.


RESULTS
Low TS protein levels in primary stage III colon tumours appeared to be associated with mucinous histology and low DPD protein levels with young age at time of randomisation. Concordance between TS and DPD expression in primary and metastatic tumours was low. No associations were found between disease-free survival (DFS) and TS or DPD protein levels. When stratified by TP 53 mutation status DFS did not differ with TS expression.


CONCLUSIONS
Expression of TS and DPD proteins is not predictive for survival in patients with stage III colon cancer treated adjuvantly with 5-FU regimens. TS protein levels did not alter the effect of TP 53 mutation status.
Westra
J L
JL
Department of Medical Genetics, University Medical Center Groningen, Groningen, the Netherlands.
Hollema
H
H
Schaapveld
M
M
Platteel
I
I
Oien
K A
KA
Keith
W N
WN
Mauritz
R
R
Peters
G J
GJ
Buys
C H C M
CH
Hofstra
R M W
RM
Plukker
J Th M
JT
D017668:Age of Onset; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil