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Clinical Cancer Research Vol. 9, 1480-1488, April 2003
© 2003 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

c-MET Expression Level in Primary Colon Cancer

A Predictor of Tumor Invasion and Lymph Node Metastases1

Hiroya Takeuchi, Anton Bilchik, Sukamal Saha, Roderick Turner, David Wiese, Maki Tanaka, Christine Kuo, He-Jing Wang and Dave S. B. Hoon2

Department of Molecular Oncology [H. T., A. B., M. T., C. K., D. S. B. H.], Division of Biostatistics, John Wayne Cancer Institute [H-J. W.], Department of Pathology, Saint John’s Health Center [R. T.], Santa Monica, California 90404, and Departments of Surgery [S. S.] and Pathology [D. W.], McLaren Regional Medical Center, Michigan State University, Flint, Michigan 48532

Purpose: Both c-MET and vascular endothelial growth factor (VEGF)-C expression are important factors in primary carcinoma progression. We hypothesized that overexpression of c-MET and/or VEGF-C mRNA in primary colorectal cancer (CRC) can predict tumor invasion and regional metastasis.

Experimental Design: The level of c-MET and VEGF-C mRNA expression was assessed using a quantitative RT-RealTime PCR assay on early stage primary CRC tumors (n = 36).

Results: The c-MET mRNA copy number ranged from 1.18 x 102 to 1.11 x 106 copies (median 5.17 x 104) per 250 ng of RNA from CRC specimens. c-MET mRNA copies in CRC specimens was significantly higher than that from normal colon mucosal epithelium (P = 0.0001). c-MET mRNA copies significantly correlated with the depth of invasion: T1 versus T2, P = 0.007; T1 versus T3/T4, P = 0.0001; T1 versus T2 versus T3/T4, P = 0.0005; and T1/T2 versus T3/T4, P = 0.011. c-MET copy number in primary CRC of N1/N2 staged patients was significantly higher than N0 cases (P < 0.03). Expression levels of c-MET mRNA were verified with immunohistochemistry analysis of c-MET protein expression in CRC specimens and normal mucosal epithelium. The VEGF-C mRNA copies of primary CRC assessed ranged from 0 to 1.65 x 105 copies (median 580). Although VEGF-C mRNA copies in CRC primary tumors were significantly higher than normal colon mucosal epithelium (P = 0.0008), it did not correlate with any major clinicopathological parameters of CRC.

Conclusions: This study indicates c-MET mRNA overexpression in primary CRC may be an important prognostic marker for early stage invasion and regional disease metastasis.




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