Expressions Of IL-24and VEGF-C In Rectal Carcinoma:Correlations With Lymphangiogenesis And Prognostic Implications

ObjectiveTo evaluate the expression of protein IL-24and VEGF-C in rectal carcinoma and detect the variation of lymphatic microvessel density marked by D2-40in tumor tissues and to investigate their relationships with clinicopathological characters of rectal cancer patients and the correlation among the three items was to be analysed too. So that to make clear the effects IL-24has on lymphangiogenesis and the expression characteristics of VEGF-C in rectal carcinoma tissue.MethodsThere are118specimens of human rectal carcinoma undergone radical resection were collected in Qilu Hospital of Shandong University from2006to2007. The expression of IL-24and VEGF-C and LVD was examed by immunohistochemical staining and LVD was calculated by the special mark of lymphatic drainage named D2-40. The relationships between clinicopathological characters of patientses and expression of IL-24, VEGF-C with and LVD was evaluated. The correlation between the three items was analyzed too. Univariate analysis and multivariate analysis were used to find the prognostis factors of patients with rectal cancer involved in our research.ResultsAll the patient or the patient’s families were contacted and the prognostic information was detailed recorded. The average age of118patients were59years, range from27years old to88years old. There are68in men and50in women. The IL-24and VEGF-C mainly localizes in the cytoplasm of rectal cancer cells, there are57(48.3%) patients with high expression of IL-24, and61(51.7%) patients express IL-24in low level. There are66(55.9%) patients with hign expression of VEGF-C, and52(44.1%) patients express VEGF-C in low level. The expression of IL-24in rectal carcinoma tissues closely associated with tumor diameter (P=0.003), local invasion (P=0.022), lymph node metastasis (P=0.017) and TNM staging (P=0.008). While the expression of VEGF-C associated with local invasion (P=0.001), lymph node metastasis (P=0.001) and TNM staging (P=0.005). D2-40mainly localizes in the cytoplasm of rectal cancer cells. The number of pLVD (peritumoral lymphatic vessel density) was higher than the number of pLVD(intratumoral lymphatic vessel density) and the difference was statistically significant. The number of pLVD in average was10.49±4.92, and the number of iLVD in average was4.65±1.32. The difference between pLVD and iLVD was statistically significant and there are no correlation between this two items. The number of pLVD higher than10was considered to be hign pLVD,56(47.5%) patients are high pLVD and62(52.5%) patients are low pLVD. The number of pLVD correlated with lymph node metastasis(P=0.001) and TNM staging (P=0.005), the pLVD of patients with lymph node metastasis (12.36±5.90) was higher than patients witn no lymph node metastasis (9.38±3.87) and the pLVD increased with the stageing of patients(pLVI) of patients with stage Ⅰ=9.04±4.62, pLVD of patients with stage Ⅱ=9.59±3.37, pLVD of patients with stage Ⅲ=12.36±5.90). There are no correlation between iLVD and clinicopathological features was found. The expression of IL-24negatively correlated with pLVD (r=0.210, P=0.023), the number of pLVD of patients with high expression of IL-24(9.53±4.56) was lower than patients with low expression of IL-24(11.39Q5.11). The espression of VEGF-C positively correlated with pLVD(r=0.400, P=0.000), the number of pLVD of patients who expressed VEGF-C in high level(11.52±5.47) was higher than patients who expressed VEGF-C in low level (9.19±9.19) and the difference was statistically significant. There is no correlation between expressions of IL-24and VEGF-C. The five-year survival rate of118patients is57.6%, patients with high expression of IL-24have higher five-year survival rate (68.4%vs47.5%, P=0.022). Patients with high expression of VEGF-C have lower five-year survival rate(43.9%vs75.0%, P=0.001). Patients with high pLVD have lower five-year survival rate(31.1%vs80.6%, P=0.000). Patients with high expression of IL-24have better prognosis and patients with high expression of VEGF-C and high pLVD have poor prognosis. Univariate analysis results showed that age (P=0.017), degree of cell differentiation(P=0.033), ymph node metastasis (P=0.005), and TNM staging (P=0.006), expression of IL-24(P=0.022), expression of VEGF-C (P=0.001) and pLVD (P=0.000) are prognostic factors of patients. Multivariate analysis showed that the expression of VEGF-C(P=0.034) and pLVD (P=0.000) are the independent prognostic factors of patients.ConclusionsHigh expression of IL-24in rectal cancer cells can inhibit the growth of tumor cell, promote apoptosis of tumor cells and prohibit lymph node metastasis by inhibiting lymphangiogenesis, IL-24may not adjust the secretion of VEGF-C to inhibit lymphangiogenesis. IL-24is an important prognostic factor of rectal cancer patients,but not independent factors. We think that expression of IL-24in rectal cancer tissues can be treated as a prognostic auxiliary index. It has a good application prospect on rectal carcinoma therapy based on its effect on inhibiting tumor cell growth and inhibiting lymphangiogenesis. Expression of VEGF-C is an independent prognostic factor of rectal carcinoma patients. The high expression of VEGF-C in rectal carcinoma tissue can promote the lymphangiogenesis. VEGF-C can be used as a treatment targets for rectal cancer, reduce the lymph node metastasis and distant metastasis of rectal carcinoma. The iLVD of rectal carcinoma did not show us any clinical significance, while the pLVD is an independent prognostic factor of rectal carcinoma patients. We can get more accurate judgment to prognosis after detection of pLVD of rectal cancer tissues.