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 cure by surgical resection. We hypothesised that in patients with occult hepatic metastases, tumour DNA might be detected in bile which could be collected during resection of the colorectal primary. To test this hypothesis, bile from the gall bladder was collected from 17 patients scheduled for resection of evident hepatic metastases (2 cm3) from a previously resected colorectal primary. Mutation analysis of the metastases identified five patients (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 amplified 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 could be ruled out by control experiments showing a high DNA isolation efficiency and high sensitivity of the mutation detection method. It is concluded that hepatic metastases, in contrast to pancreatic cancers, do not (regularly) shed mutated DNA into the bile. Hence, molecular screening of bile seems of only limited clinical value for the detection of occult liver metastases.