Expression of HGF and VEGFR-3 in Colorectal Carcinoma and Their Role in Lymphangiogenesis and Lymphatic Metastasis

Objective To investigate the role of hepatocyte growth factor(HGF) and vascular endothelial growth factor receptor 3 (VEGFR-3) in lymphangiogenesis and lymphatic metastasis of colorectal carcinoma by analyz the expression of HGF and VEGFR-3, and calculating lymphatic vessel density (LMVD) in colorectal carcinoma. Methods The expression of HGF and VEGFR-3 in specimens of 52 colorectal carcinoma, 20 colorectal polyps tissues and 20 colorectal normal tissues was evaluated by immunohistochemistry utilizing strept-avidin-biotin complex. LMVD in colorectal carcinoma was calculated by using podoplanin as the specific marker of lymphatic endothelium. And the clinicopathological features of colorectal carcinoma were analyzed. Results （1）The stainings of brown and filemot in cytoplast were observed as the positive expression of HGF and VEGFR-3 proteins.The positive rate(75%,67.5%) and mean value [(0.36±0.07）,（0.41±0.10)] of HGF and VEGFR-3 expressions in specimens of colorectal carcinoma were significantly higher than those of the colorectal polyps tissues[25%,30%；(0.24±0.06),(0.28±0.03)] and the normal bowel tissues(15% 10%; 0.23±0.06 0.21±0.03)(P<0.05).The LMVD of colorectal carcinoma was also significantly higher than those of the colorectal polyps tissues and the normal bowel tissues[(4.13±1.99) vs. (2.59±1.46) vs. (2.40±1.44),P<0.01]. (2)A significant correlation was found between either two of LMVD, the mean value of HGF and VEGFR-3 in specimens of colorectal carcinoma. The positive expression of HGF was found in 39 cases of colorectal carcinoma, and their mean LMVD was higher than that in the negative ones [(4.25±2.13) vs. (2.73±1.54), t=3.051, P=0.003]. The positive expression of VEGFR-3 was observed in 35 cases of colorectal carcinoma, and their mean LMVD was higher than that in the negative ones [(3.79±1.26) vs. (2.64±1.32),t=3.235,P=0.002]. (3)The expression of HGF,VEGFR-3 and LMVD in colorectal carcinoma was no correlation with age,gender and degree of differentiation, but significant correlation with Dukes'staging(P=0.034,P=0.021,P=0.006) and lymph node metastasis(P=0.015,P=0.012,P=0.001). Conclusion The positive expression of HGF is related with colorectal cancer lymphangiogenesis and lymphatic metastasis. It seems that HGF induces lymphangiogenesis indirectly through VEGF-C,D/VEGFR-3 signaling pathway and contributes to lymphatic metastasis in colorectal carcinoma.