Immunohistochemical Demonstration of Thymidylate Synthase (Ts), P53 Protein and BCl-X_L Protein in Colorectal Cancer with Preoperative Peroral Chemotherapy: Ts as Marker of Unresponsiveness To 5-Fluorouracil

High expression of thymidylate synthase (TS), p53 protein and bcl-X_L protein has been suggested to be associated with chemoresistance of colorectal malignancies. The significance of TS, p53 protein and bcl-X_L protein as predictive parameters of effects of 5-fluorouracil (5-FU)-based chemotherapy on colorectal cancers was evaluated. Immunoperoxidase staining of TS, p53 protein and bcl-X_L protein was performed on formalin-fixed, paraffin-embedded, opsied and resected specimens from 37 patients with advanced colorectal cancers, preoperatively treated with 5-FU derivatives per os. Suitable antigen retrieval was applied to the respective markers. Histologically, six tumors responded to the chemotherapy, while the remaining 31 tumors did not. Thirty- one control colorectal cancer cases without preoperative treatment were also analyzed. When more than one third of the cancer cells were stained, the lesions were considered high for antigen expression. High TS expression in the resected tumors was seen in 23 (74%) of 31 histologic non-responders but none in six responders. TS expression in preoperative biopsies and resected specimens was concordant in 80% of cases when two or more biopsy specimens were available. The rate of high TS expression was comparable in the control non-treated group. There was no difference between chemotherapeutic effects and the expression of p53 protein or bcl-X_L protein. Chemoresistance to 5-FU and 5-FU derivatives can be predicted by immunohistochemical detection of high TS expression in biopsy samples. This provides us with a useful guide for preoperative selection of patients unresponsive to 5-FU-based chemotherapy. Expression of p53 protein and bcl-X_L protein is unsatisfactory for predicting the 5-FU resistance.