| Lung cancer is one of the leading cause related deaths in the world, because the number of deaths due to lung cancer is more than 1,180,000 annually. About 80% of lung cancer is non-small cell cancer. Approximately 65% of the patients are in the advanced stage or have metastases when diagnosed. Now TNM staging system is widely used to predict prognosis of NSCLC patients, but those patients within the same stage may have very different surivivals. So better prognostic index is needed.Background and Objective: Angiogenesis was considered to be a crucial process both for tumor growth and for metastatic dissemination, with acquisition of an angiogenic potential being a necessary step in tumor progression. Whether angiogenesis was to be or not depended on the balance between the pro-angiogenic molecules and the anti-angiogenic molecules. Inhibition of angiogenesis had become a primary target for antineoplastic therapy, and molecules acting at different levels on the angiogenic cascade reduced or even suppressed growth of some tumors. Recent reports suggested that vascular endothelial growth factor (VEGF) was the most potent angiogenic factor. On the other hand, increased tumor microvessel density (MVD) was associated with poor outcome in several malignant tumors, including NSCLC. Poblet reported different vascular markers could be used to identify the heterogeneity of tumor angiogenesis and its different aspects of characteristics, CD34 only expressed in differentiation endothelial cells while CD31 could be expressed in differentiated and undifferentiated endothelial cells. Tumor microvessels could be divided into two categories: differentiation blood vascular (CD34 +) and undifferentiated blood vessels (CD31 + / CD34-). The role of VEGF and MVD as biological indicators were still controversial, and the ralation between different categories of tumor microvessels based on the expression of different vascular markers and prognosis had yet to reach a conclusion in NSCLC. In this study we used immunohistochemistry to investigate expression of VEGF,measure MVD by CD34 and CD31, explore their relationships with clinical parameters and prognosis and evaluate the association between expression of VEGF and different types of blood vessels with the patients' outcomes.Methods: Immunohistochemical staining was used to detect the expression of VEGF in 51 cases of NSCLC and 21 normal lung tissues. The microvessels were labeled with anti-CD34 monoclone antibody and anti-CD34 monoclone antibody to assess microvessel density. Compare expression of VEGF and two distinct types of microvessels with clinical pathological characteristics. Evaluate the correlation between these two factors and prognosis.Results:1 In the 21 normal lung tissues, were 19.0% (4/21). While in the 51 cases of NSCLC, the positive rates expression of VEGF were 78.5%(40/50). The difference is significant statistically (P<0.05).2 The expression of VEGF were insignificantly to patient age, sex, smoking history, pathological type, differentiation grade, tumor size , lymph node metastasis and TNM stage (P>0.05). The positive rate of the cases of advanced clinical stage (III～IV) was 89.5%, while early clinical stage (I～II) was 71.9%, but the difference was no statistically significant.3 In these cases, the microvessel density measured by CD34 was from 11.67 to 35.67 every high-power field and the mean is 19.42. MVD measured by CD31 was from 24.00 to 103.33 every high-power field and the mean is 56.48.Differented microvessel density was closely related to lymph node metastasis and TNM stage(P<0.05), but insignificantly to patient age, sex, smoking history, pathological type, differentiation grade and tumor size (P>0.05). And undifferented microvessel density was closely related to TNM stage(P<0.05), but not with the other factors. 4 The survival rate of higher VEGF expression group was significantly lower than low-expression group, Log-rank test, x~2=9.642, P=0.002, the difference was statistically significant (P<0.05). The survival rate of higher MVD of undifferentiated vascular group was significantly lower than lower group, Log-rank test, x~2=4.611, P=0.032 the difference was statistically significant (P<0.05). The survival rate of higher MVD of differentiated vascular group was significantly lower than lower group, Log-rank test, x~2=4.782, P=0.029, the difference was statistically significant (P<0.05).5 The relevance between VEGF expression and microvessel density of two distinct types of blood vessels was no statistical significance (r=-0.108, P=0.449) (r=0.88 , P = 0.539). The relevance between undifferented and differented microvessel density was a negative correlation(r=-0.364, P=0.009).Conclusion: We found that the higher expression of VEGF suggested the worse the prognosis, the shorter survival time in NSCLC. Increased both undifferentiated vessel MVD and differentiated MVD significantly correlated with higher pathologic grades and shorter patient survival. VEGF expression had no significant correlation with two distinct types of blood vessel. |
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