c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases.
OBJECTIVE
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.


METHODS
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 10(2) to 1.11 x 10(6) copies (median 5.17 x 10(4)) 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: T(1) versus T(2), P = 0.007; T(1) versus T(3)/T(4), P = 0.0001; T(1) versus T(2) versus T(3)/T(4), P = 0.0005; and T(1)/T(2) versus T(3)/T(4), P = 0.011. c-MET copy number in primary CRC of N(1)/N(2) staged patients was significantly higher than N(0) 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 10(5) 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.
Takeuchi
Hiroya
H
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Bilchik
Anton
A
Saha
Sukamal
S
Turner
Roderick
R
Wiese
David
D
Tanaka
Maki
M
Kuo
Christine
C
Wang
He-Jing
HJ
Hoon
Dave S B
DS
D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
D017931:DNA Primers; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D012313:RNA; D019859:Proto-Oncogene Proteins c-met