Clinical value of bile for the detection of mutant K-ras from colorectal liver metastases

In 25% of patients diagnosed with colorectal cancer, hepatic metastases are not detected at presentation of the colorectal primary but develop during follow-up. Early detection of these metastases may improve the chance of cu re by surgical resection. We hypothesised that in patients with occult hepa tic metastases, tumour DNA might be detected in bile which could be collect ed during resection of the colorectal primary. To test this hypothesis, bil e from the gall bladder was collected from 17 patients scheduled for resect ion of evident hepatic metastases (>2 cm(3)) from a previously resected col orectal primary. Mutation analysis of the metastases identified five patien ts (34%) with a K-ras gene mutation in the tumour tissue. These cases were selected for bile analysis for mutant K-ras. Non-mutated DNA could be ampli fied from all the bile samples, but mutant K-ras could only be detected in bile from one patient. False negative results due to technical deficits cou ld be ruled out by control experiments showing a high DNA isolation efficie ncy and high sensitivity of the mutation defection method. It is concluded that hepatic metastases, in contrast to pancreatic cancers, do not (regular ly) shed mutated DNA into the bile. Hence, molecular screening of bile seem s of only limited clinical value for the detection of occult liver metastas es.