Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases

Aims: The liver is a frequent site of metastases from colorectal cancer. Wh ile these lesions are potentially amenable to surgical resection, they are usually very aggressive, and recurrence is frequent. Mutations of the proto -oncogene K-ras are thought to impart a strong growth signal to tumour cell s and are closely associated with the development of malignancies of the co lon and rectum. Hepatic metastases from colorectal cancer have notably elev ated proliferative rates. The present study was performed to investigate th e relationship between proliferation or K-ras mutation and prognosis follow ing curative resection of colorectal liver metastases. Methods: Colorectal liver metastases from 41 patients undergoing curative h epatic resection were examined for proliferation status and presence of K-r as mutations. The proliferative activity was assessed by Ki-67 immunohistoc hemistry. DNA from the same tissue samples was screened for point mutations in codon 12 of the K-ras gene using a novel microplate-based allelic-speci fic hybridization assay. Ki-67 scores and K-ras status were then related wi th patient survival as determined through retrospective analysis. Results: Median survival was 40 months. Patients with high Ki-67 scores (gr eater than or equal to 50%) had significantly shorter median survival compa red with those with low scores (30 vs 44 months, log-rank P=0.02). A high K i-67 score was an independent negative prognostic factor by multivariate re gression analysis (relative risk = 3.04, P = 0.036). K-ras point mutations were detected in 6/41 patients (15%), but mutational status did not correla te with Ki-67 score or survival. Conclusions: These findings suggest that the tumour proliferative index is a useful predictor of aggressive tumour behaviour and an indicator of patie nt survival. The presence of K-ras mutations does not appear to correlate w ith tumour proliferation status or patient survival. (C) 2001 Harcourt Publ ishers Ltd.