Expression Of C-met And Its Role In The Initiation And Development Of Colorectal Carcinoma

The proto-oncogene C-MET, which encodes the hepatocyte growth factor/scatter factor (HGF/SF) receptor C-met, is frequently expressed in the surface of epithelial cells. The tyrosine kinase receptor C-met together with its ligand HGF/SF regulates cellular proliferation, migration and differentiation during organ development and tissue homeostasis. Overexpression of C-met has been shown to be associated with poor prognosis in a number of solid tumors. In colorectal cancer (CRC), however, the relationship between C-met protein level and clinical character has been controversial, which was mostly determined by the lackage of the reliable C-met antibody for evaluating C-met expression.Objective To investigate the expression level of C-met in human colorectal cancer and the relationship between C-met expression levels and clinicopathological factors, and explore the effect of C-met in the process of invasion and C-met astasis in CRC.Methods The expression levels of C-met in formalin-fixed and paraffin-embedded (FFPB) specimens from78primary CRC and6adenoma were estimated by IHC using C-met monoclonal antibody. The relationship between C-met expression levels and clinicopathological factors was evaluated.Results (1)C-met cytoplasm staining results of78primary CRC:positive,46cases; moderate,22cases (the rates of positive expression were59%and28.2%, respectively); negative,10cases (12.8%). C-met cytoplasm staining results of6adenoma:positive,2cases; moderate,2cases; negtive,2cases. Normal colon epithelium cells showed negative or weak cytoplasm staining. No significant statistical differences were observed in the cytoplasm staining intensity across clinical subtypes of colorectal cancer. (2)C-met membrane staining results of78primary CRC:When membrane immunostaining score3was considered as positive and≤2as negative, C-met membrane expression may be associated with the lymphatic early-stage invasion and C-metastasis of CRC. stage Ⅲ and stage Ⅰ were tend to present higher membrane C-met staining than cytoplasm C-met staining, while the cytoplasm C-met staining were mostly appeared in stage Ⅱ and stageⅣ patients.Conclusion The data from this study demonstrated the specificity and reproducibility of C-met for assessing C-met in CRC primary tumor. The membrane distribution of C-met in CRC primary tumor may predict tumor regional C-metastatic potential.