Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome.

Kammula US, Kuntz EJ, Francone TD, Zeng Z, Shia J, Landmann RG, Paty PB, Weiser MR

Surgery Branch, National Cancer Institute, Bethesda, MD, USA.

INTRODUCTION/HYPOTHESIS: Over-expression of the c-Met receptor tyrosine kinase has been described in a variety of cancers and implicated in tumor progression. Unlike some solid tumors, current evidence indicates that c-Met activation in colon cancer is unrelated to gene mutation, is ligand dependent, and occurs via a paracrine fashion. We hypothesize that over-expression of the c-Met receptor and its ligand, hepatocyte growth factor (HGF) in the tumor microenvironment is associated with tumor progression and metastases. METHODS: Primary tumor c-Met and HGF mRNA expression was analyzed in 60 colon adenocarcinomas. Receptor and ligand expression was analyzed for correlation and association with clinicopathologic features and outcome. RESULTS: Compared to adjacent normal mucosa, 69% and 48% of tumors showed a greater than 2- and greater than 10-fold elevation in c-Met mRNA, respectively. Elevated HGF mRNA was noted in 47% of tumors with 19% having a greater than 10-fold increase. Tumor c-Met expression was correlated with HGF expression, and a cohort of 33 patients could be defined with both low c-Met and HGF expression. Compared with the 27 tumors with either high c-Met or HGF, the cohort with low c-Met and HGF expression had fewer nodal and distant metastases as well as improved overall survival (HR=2.3, p<0.05). CONCLUSION: Evaluation of the c-Met receptor in context of ligand, HGF, allows identification of a metastatic phenotype that correlates with advanced stage and poor survival. c-Met and HGF co-expression in the tumor microenvironment could be useful in the molecular staging of colon cancer and viable therapeutic targets.

Published 6 March 2007 in Cancer Lett, 248(2): 219-28.
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