Immunohistochemical determination of p53 protein does not predict clinicalresponse in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil-leucovorin combination

Background: We assessed the hypothesis that a compromised p53 function coul d account for the non response of colon cancer patients with low thymidylat e synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU)-leucovor in (LV) combination. Patients and methods: The study population consisted of 41 patients with un resectable metastatic colon cancer, homogeneosuly, treated with bolus 5-FU and LV. Results: Twenty-seven patients (66%) showed high levels of TS expression. T he difference in the proportion of objective responses between patients wit h low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was sta tistically significant (P = 0.0001, chi-square test). p53 nuclear overexpre ssion was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients w ith low TS expression. Conclusions: p53 status measured by immunohistochemistry does not seem to b e useful to identify unresponsive patients with low TS expression.