Thymidylate synthase (TS), a critical enzyme
in 5-Flourouracil (5-FU) metabolism, plays a significant
role in predicting survival and therapeutic response in
colorectal cancer (CRC) patients. Present study evaluated
prognostic as well as predictive utility of TS VNTR
polymorphism, TS mRNA expression and its protein level
in CRC patients. Total 143 CRC patients were enrolled.
TS VNTR polymorphism and TS mRNA expression were
studied by PCR and semiquantitative RT-PCR,
respectively.With regard to prognosis, a trend of
reduced relapse-free survival (RFS) was noted with
carriers of 3R allele (2R/3R+3R/3R) in rectal cancer
subgroup (P=0.065). Further, high TS mRNA expression
was associated with unfavorable RFS in total CRC
patients (P=0.038), as well as in the subgroups of early
stage (P=0.073), rectal cancer (P=0.059) and single drug
5-FU treated patients (P=0.029). On the other side, low
TS protein expression showed poorer RFS (P=0.050) and
overall survival (OS) (P=0.071) in colon cancer subgroup.
It can be concluded that TS could be beneficial prognostic
and predictive marker to identify patients with poor
clinical outcome and thus might be useful to choose
effective treatment modalities for CRC patients.
Keywords : TS, Colorectal Cancer, VNTR polymorphism, mRNA, Protein, 5-FU, Immunohistochemistry, Prognosis