Expressions of Vascular Endothelial Growth Factor (VEGF)-D and VEGF Receptor-3 in Colorectal Cancer: Relationship to Lymph Node Metastasis

Angiogenic factors play a major role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)- D is a ligand for VEGF receptor-3 (VEGFR-3/Flt-4), which mainly expressed on the lymphatic endothelium. Recent experimental studies have shown that VEGF-D induces tumor lymphangiogenesis and promote metastatic spread of tumor cells via lymphatic vessels. However, the contribution of VEGFD to lymph node metastasis in human colorectal cancer is less understood. We therefore examined VEGF-D and VEGFR-3 expression in patients with colorectal cancer. Sections of formalin-fixed and paraffin-embedded specimens from 76 colorectal cancers were immunohistochemically stained for VEGF-D and VEGFR-3. Staining for VEGF-D was positive in the cytoplasm of tumor cells in 43 of 76 examined tumors (56.6%). Staining for VEGFR-3 was positive in endothelial cells in 38 (50.0%) tumors. Univariate analysis showed that both VEGF-D and VEGFR-3 expressions correlated significantly with lymph node metastasis, histological type and depth of tumor invasion. However, logistic regression analysis indicated that VEGF-D expression, but not that of VEGFR-3, was an independent predictor for lymph node metastasis. Our data suggest that VEGF-D plays an important role in lymph node metastasis in colorectal cancer

Elevated Expression of Poly(ADP-Ribose) Polymerase-1 is Associated with Liver Metastasis in Colorectal Cancer.

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) and its subsequent cleavage are early markers of apoptosis. PARP-1 is associated with DNA repair and so chromosome stability, cell cycle regulation, as well as tumorigenesis. To investigate the role of PARP-1 expression in colorectal carcinoma and its metastasis of liver, we compared the expression of PARP-1 in primary colorectal cancers with (n=15) and without liver metastasis (n=17) using a semi-quantitative reverse transcription - polymerase chain reaction. We also examined the expressions of poly(ADP-ribose) (PAR) and p53 in these tumors by immunohistochemistry. A significantly higher PARP-1 mRNA expression was noted in tumors with liver metastasis than those without liver metastasis (p<0.01). Colorectal cancers positively stained for p53 exhibited significantly higher PARP-1 mRNA expression than p53-negative tumors (p<0.01). The PAR labeling index (LI) of tumors with metastasis (0.33 ﾂｱ 0.33) was not significantly different (p=0.35) from that of tumors without liver metastasis (0.38 ﾂｱ 0.19). p53-positive tumors tended to have higher PAR LI levels than p53-negative tumors (p=0.08). Our findings suggest that PARP-1 may contribute to liver metastasis due to its DNA repair activity, resulting in survival of the tumor cells with accumulation of metastaticrelated gene\u27s damages. Detailed analysis of PARP-1 may be useful in cancer research and/or cancer therapy