Thymidylate synthase and cyclin D1 protein expression in lymph node negative colorectal cancer: role as prognostic factors?
Thymidylate synthase (TS) is an enzyme for DNA-synthesis and the target for 5-fluorouracil whereas cyclin-D1 plays a critical role in the progression of cells through the G1 phase of the cell-cycle. There is evidence that expression of these markers may predict the outcome of patients with colorectal cancers. The aim of this study was to examine the prognostic value of TS and cyclin D1 protein expression in patients with node negative colorectal cancers. TS and cyclin D1 protein expression from 140 patients with UICC stage I and II colorectal cancer was analyzed by immunhistochemistry in paraffin-embedded primary tumour specimens. The 1-, 5- and 10-year overall-survival rates were 96%, 86% and 71%, respectively. Tumour stage and recurrence were associated with overall-survival. Low- and high TS immunoreactivity was present in 68 (48%) and 72 (52%) of cancers, respectively. Low- and high cyclin D1 immunoreactivity was present in 98 (70%) and 42 (30%) of the cancers, respectively. Patients (n=72) with high TS expressing tumours had a worse overall-survival than patients (n=68) with low TS expressing colorectal cancers (p=0.011). No difference in overall-survival was seen between patients with high and low cyclin D1 expressing cancers. TS may be helpful as a prognostic marker in lymph node negative colorectal cancer.