To date the response rates to biomodulated 5-fluorouracil in patients with metastatic or unresectable colorectal carcinoma have been varied. Potentially responsive patients are difficult to identify and treatment schedules are both expensive and toxic. Thus, any method that could be used to predict patient response would be both clinically and economically valuable. Increased p53 protein levels have previously been shown to correlate with disease progression in a series of colorectal carcinoma patients treated with 5-FU/folinic acid biomodulated chemotherapy. In addition to mutation of the p53 tumour suppressor gene, mutation of the K-ras gene at codon 12 has also been shown to be a frequent occurrence in the step-wise progression from normal colonic mucosa to adenocarcinoma. Oncogenic activity in the ras family has recently been shown to correlate with decreased levels of apoptosis and thus increased resistance to both radiation and certain chemotherapeutic agents. The aim of the present study was therefore to investigate if a correlation existed between mutation of the K-ras gene at codon 12 and disease progression in the series of colorectal carcinoma patients previously evaluated for levels of p53 protein expression. Response to 5-FU/folinic acid was assessed radiologically by CAT scan (WHO criteria) and clinically by Karnofsky performance scale (KPS) 3 months after the initial treatment. The presence of a K-ras gene mutation was assessed with radiolabelled oligonucleotide probes on amplified patient DNA, dot blotted on to a nylon membrane. Fifty-two patients were assessed and 25% were found to possess mutations at codon 12 of their K-ras gene. In contrast to increased levels of p53 protein, K-ras mutation at codon 12 did not correlate with disease progression when assessed either radiologically or clinically.

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