C-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases

Abstract

The c-Met proto-oncogene encodes a receptor tyrosine kinase (TK) that promotes invasive tumor growth and metastasis. Recent studies show that the presence of c-Met gene amplification is predictive for selective c-Met TK inhibitors in gastric cancer and lung cancer. In this study, we utilized a highly quantitative PCR/ligase detection reaction technique to quantify c-Met gene copy number in primary colorectal cancer (CRC) ( N = 247), liver metastases ( N = 147), and paired normal tissues. We identified no differences in c-Met gene copy number between normal colonic mucosa and liver tissue. However, mean c-Met gene copy number was significantly elevated in CRC compared with normal mucosa ( P < 0.001), and in liver metastases compared with normal liver ( P < 0.001). Furthermore, a significant increase in c-Met was seen in liver metastases compared with primary CRC ( P < 0.0001). c-Met gene amplification was observed in 2% (3/177) of localized cancers, 9% (6/70) of cancers with distant metastases ( P < 0.02), and 18% (25/147) of liver metastases ( P < 0.01). Among patients treated by liver resection, there was a trend toward poorer 3-year survival in association with c-Met gene amplification ( P = 0.07). Slight increases in c-Met copy number can be detected in localized CRCs, but gene amplification is largely restricted to Stage IV primary cancers and liver metastases. c-Met gene amplification is linked to metastatic progression, and is a viable target for a significant subset of advanced CRC.