P53 PROTEIN OVEREXPRESSION AND RESPONSE TO BIOMODULATED 5-FLUOROURACIL CHEMOTHERAPY IN PATIENTS WITH ADVANCED COLORECTAL-CANCER

Biomodulated 5-fluorouracil (5-FU) chemotherapy may limit disease prog ression in up to 50% of patients with metastatic or unresectable carci noma of the colorectum. However, treatment is expensive and may be tox ic. Thus any predictors of response mag be clinically and economically valuable. The p53 gene is mutated in more than 50% of colorectal tumo urs, usually resulting in p53 overexpression. It may regulate cell cyc le progression and cellular response to DNA damage. The principal anti cancer activity of 5-FU is due to its ability to induce DIVA damage. F ifty-nine patients received bolus intravenous 5-FU/folinic acid ol er 3 months. Response was assessed by CAT scan (WHO criteria). p53 protei n overexpression was determined immunohistochemically from paraffin se ctions of the original primary tumour and resected metastases. Tumour over expression of p53 protein was associated with a lower rate of rep onse and a higher rate of deterioration both radiologically (P<0.03) a nd clinically (P<0.05, chi(2) test for trend), but did not predict sur vival from start of treatment. Response was unrelated to age, sex, tum our grade, site of disease or chemotherapy schedule. Tumour p53 protei n overexpression alone cannot be used to select advanced colorectal ca ncer patients for chemotherapy but may be useful in association with o ther markers of tumour biology.