Expression Of Secondary Lymphoid Tissue Chemokine CCR7 And VEGF-C In Colorectal Adenocarcinoma

Background and Objectives Colorectal carcinoma is one of the most common gastroenteric malignant diseases. Vascular invasion and lymph nodes metastasis are closely associated with the prognosis of patients with colorectal carcinoma. However, little is known about the mechanisms of tumor cells migration and metastasis. Chemokines belong to the small molecule chemoattractive cytokine family. They can mediate lymphocytes trafficking, regular angiogenesis, maintain immunity stabilization and take part in the development of secondary lymphoid organs. Chemokines and their receptors play important roles in tumor growth and angiogenesis.Secondary lymphoid tissue chemokine (SLC) is the member of CC chemokine. SLC and its receptor CCR7 play crucial roles in the homing of lymphocytes into the secondary lymphoid organs. They can also recruit dendritic cells (DCs) which capture antigen, and naive T cells to lymphoid tissue where DCs may present antigen to T cells to active immune response. However, the role of chemokines and their receptors in tumor metastasis has only recently been explored .Vascular endothelia growth factor C (VEGF-C) is a member of the VEGF/PDGF family and acts as highly specific lymphangiogenic factor. Studies have shown that it can induce tumor lymphangiogenesis and direct metastasis to the lymphatic vessels and lymph nodes. High expression of VEGF-C has recently been shown to closely correlate with lymphatic involvement and lymph nodes metastasis in many malignant tumors.In this study, immunhistochemistry and Hybridization in situ technique were used to investigate expression of SLC mRNA, CCR7 protein and VEGF-C protein in human colorectal carcinoma and their relationship to other clinical pathological variables.Materials and Methods (D 41 patients who underwent surgery for colorectal carcinomas at the First Affiliate Hospital of Zhengzhou Universary between 2003-2004, were included in the study. Samples were taken from tumor site and paracancerous tissues (^5cm), which were confirmed pathologically as normal colorectal mucosa. None of the patients had received chemotherapy or radiation therapy before surgery.(2) The expression of SLC mRNA was examined by use of Hybridization in situ . The expression of CCR7 protein and VEGF-C protein were examined by use of SP immunhistochemistry.(3) The data was analyzed by software SPSS 10.0, x 2-test and Spearman correlation were used to analyze the difference between groups, a =0.05 was considered as statistically significant value.Results (D There was no expression of SLC mRNA in colorectal carcinoma tissues; there was no or faint expression of SLC mRNA in adjacent normal colorectal mucosa. The positive expression rate of SLC mRNA in the metastic negative lymph nodes 78.57%(22/28) was significantly higher than that metastic positive ones 12.50%(3/24) (P < 0.05).(2) In adjacent normal colorectal mucosa, no staining in cytoplasm for CCR7 protein was found. The percentage of patients positive for CCR7 protein in colorectal carcinoma cells was 58.54% (24/41) , and was correlated to depth of invasion, Dukes stage and lymph nodes metastasis (P < 0.05) . There was significant difference of the positive expression rate of CCR7 protein between the serosal infiltration group 82.61%(19/23 ) and the subserosa group 27.78% (5/18) (P < 0.05). There was a higher positive expression rate of CCR7 protein in the C+D group 80.95% (17/21) than that in the A+B group 35.00% (7/20) (P < 0.05). There exited significant difference of the positive expression rate of CCR7 protein between the lymph node metastasis negative group 35.00%(7/20)and the lymph node metastasis positive group 80.95% (17/21 )(P < 0.05). But its relation to histological grade was not significant (P>0.05) .(3) In adjacent normal colorectal mucosa, no staining in cytoplasm for VEGF-C protein was found. The percentage of patients positive for VEGF-C protein in colorectal carcinoma cells was 36.59% (15/41) , and was correlated to depth of invasion, Dukesstage and lymph nodes metastasis (P < 0.05). There was significant difference of the positive expression rate of VEGF-C protein between the serosal infiltration group 56.52% (13/23) and the subserosa group 11.11% (2/18) (P < 0.05). There was a higher positive expression rate of VEGF-C protein in the C+D group 52.38% (11/21) than that in the A+B group 20.00% (4/20) (P < 0.05). There was significant difference of the positive expression rate of VEGF-C protein between the lymph node metastasis negative group 15.00% (3/20) and the lymph node metastasis positive group 57.14% (12/21) (P < 0.05). But its relation to histological grade was not significant (F>0.05). ? There was closely correlation of the positive expression between CCR7 protein and VEGF-C protein in colorectal carcinoma tissues (P<0.05) . Moreover, the positive expression of CCR7 protein was higher than that of VEGF-C protein (P < 0.05).Conclusions ? SLC may play an important role in the development of colorectalcarcinoma and lymph node metastasis.(D The overexpression of CCR7 protein and VEGF-C protein in colorectal carcinomatissues was positively correlated to the clinicopathologic state such as depth of invasion,Dukes stage and lymph nodes metastasis. Tumor with overexpression of CCR7 andVEGF-C is more likely to have lymph nodes metastasis. They may be important indexesfor predicting the risk of colorectal carcinoma development and become new targets forthe treatment of colorectal carcinoma.(D The positive expression of CCR7 protein in colorectal carcinoma was higher thanthat of VEGF-C protein. CCR7 may be a better biological marker to foresee the lymphnode metastasis.? The combined examination of CCR7 and VEGF-C expression in endoscopic biopsyspecimens may aid in detecting lymph node metastasis.