Clinical significance of K-ras mutations in intraoperative tumor drainage blood from patients with colorectal carcinoma

Background: Recurrent and metastatic carcinoma of the colorectum remains a major problem. This may be ascribed to the presence of micrometastasis at diagnosis. The purpose of this study was to analyze prospectively the clinical value of detecting K-ras mutations in the perioperative circulating blood from patients with colorectal carcinoma. Methods: Twenty-four patients whose tumor carried mutations in codon 12 of the K-ras gene were studied for the presence of cancer cells in perioperative blood samples, in particular, tumor drainage samples. A detection assay using CD45 immunomagnetic separation plus nested mutant allele specific amplification (MASA) was performed. Results: K-ras mutations in CD45 negative cells in tumor drainage blood were detected in 7 (29.2%) of 24 patients. There was no significant relationship between the presence of a K-ras mutation and clinicopathological features. Four (57.1%) of the seven patients with a positive K-ras mutation in drainage blood had early recurrent disease. Of the 17 patients with no K-ras mutation, none developed metastatic disease. The recurrence rate of the K-ras mutation positive group was higher than that of the K-ras mutation negative group (P < 01). There was a significant difference, regarding prognosis, between K-ras mutation positive and negative groups (P < .01). Conclusions: This preliminary study demonstrates that the detection of circulating cancer cells in the tumor drainage blood by our new assay system may provide a predictor of recurrence and metastasis of colorectal cancer.