Significance of Thymidylate Synthase Expression in Colorectal Cancer

Min, Byung Wook; Hong, Jeong Hoon; Lee, Kyung Bum; Moon, Hong Young

Abstract

PURPOSE: Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU). It is known that TS is related to response, and resistance, following chemotherapy due to colorectal cancer. The object of this study was to identify the clinical significance of TS as a prognostic factor, and its influence on 5-FU based chemotherapy in colorectal cancer.
METHODS
We performed a retrospective study on 105 consecutive patients who were operated on, at the Department of Surgery, Korea University, College of Medicine, for colorectal cancer between Jan. 1994 and Dec. 1995. We used formalin fixed, paraffin embedded tissues of resected specimens for our study. For the semi-quantitative study, the specific monoclonal antibody, TS106, was used for immunohistochemical staining. Interpretation of the immunohistochemical staining, for intratumoral TS expression, was divided into 4 grades: intensity 0, 1 , 2 , 3 were defined as, a total absence of TS immuno staining, less than 25%, 25~50% and more than 50%, of tumor staining positive, respectively. Grades 0, 1 , and 2 were regarded as low TS expression groups and 3 regarded as a high TS expression group. We then analyzed 5-year survival rates, according to Dukes' stage, and whether systemic chemotherapy was performed, or not, according to TS expression.
RESULTS
Of the 105 patients, 91 (86.7%) showed TS expression, 21 (20%) with high TS expression and 84 (80%) were low TS expression. As Dukes' stage advanced, the incidence of high expression of TS increased (P=0.048). In Dukes' stage B2, 5-year survival rates for the low TS expressed group was better than for the high TS expressed group (P=0.0052). In patients who received postoperative chemotherapy, 5-year survival rates for the low TS expressed group were better than for the high TS expressed group (P=0.049).
CONCLUSION
These data suggest the expression of intratumoral TS, studied by immunohistochemical staining, is relevant to the prognosis of colorectal cancer, especially Dukes' stage B2. It is also related to the response rate of 5-FU based systemic chemotherapy in colorectal cancer.