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Clinical Significance of K-Ras Mutations in Intraoperative Tumor Drainage Blood From Patients With Colorectal Carcinoma

From the Department of Surgery (TE, HI, KS, TU, MM), Medical Institute of Bioregulation, Kyushu University, Beppu, Japan; Department of Surgery (HU,), Oita Prefectual Hospital, Oita, Japan; Division of Digestive Disease and Nutrition (GFB), University of Massachusetts Medical School, Worcester, Massachusetts; and Department of Surgery I (TE, SK), Faculty of Medicine, Oita Medical University, Oita, Japan.

Correspondence: Address correspondence and reprint requests to: Masaki Mori, MD, Department of Surgery, Medical Institute of Bioregulation, Kyushu University 4546, Tsurumihara, Beppu 874-0838, Japan; Fax: 81-977-27-1651; E-mail: mmori{at}tsurumi.beppu.kyushu-u.ac.jp

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.

Key Words: K-ras mutation • MACS system • Prognosis • Drainage blood • Colorectal carcinoma

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