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

Cancer Lett. 2008 Jul 8;265(2):258-69. doi: 10.1016/j.canlet.2008.02.049. Epub 2008 Apr 18.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Amplification*
  • Gene Dosage
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-met / genetics*

Substances

  • Proto-Oncogene Proteins c-met