Quantification of vascular endothelial growth factor-C and its receptor-3 messenger RNA with real-time quantitative polymerase chain reaction as a predictor of lymph node metastasis in human colorectal cancer

Background. This study was undertaken to determine whether vascular endothelial growth factor-C (VEGF-C) and the expression of its receptor VEGF receptor-3 (VEGFR-3) are correlated with lymph node metastasis in human colorectal cancer and whether their expression levels might be used to predict lymph node metastasis. Methods. Fifty-three surgical specimens of colorectal cancer with (n = 24) or without (n = 29) lymph node metastasis were studied. The messenger RNA (mRNA) expression of VEGF-C and VEGFR-3 was quantified with a new method for kinetic quantitative polymerase chain reaction (PCR), real-time quantitative (RTQ) reverse transcriptase-PCR. In addition, their protein expressions were assessed immunohistochemically. Results. The VEGF-C mRNA level in primary tumors correlated with VEGF-C protein expression, lymph node metastasis, and lymphatic invasion. Sixteen of 24 patients with lymph node metastasis showed VEGF-C mRNA overexpression. Morphologically, VEGF-C protein expression in primary tumors showed a statistically significant relationship with lymph node metastasis and lymphatic invasion. Conclusion. Real-time quantitative reverse transcriptase-PCR is a sensitive method for detection and quantification of VEGF-C and VEGFR-3 mRNA expression. Furthermore, the expression levels of VEGF-C mRNA and protein in colorectal cancer are correlated with lymph node metastasis and lymphatic invasion. (Surgery 2003;133:300-8.)