Vascular Endothelial Growth Factor Expression In Stage I_A Non-Small Cell Lung Cancer And Clinical Significance

Background and Objective: Lung cancer is the main cause of cancer deaths in our country.The long survival rate for NSCLC has remained stable,suggesting that there has been a little progress in treatment[1].Over the last several decades,the tumor-node-metastasis staging system and tumor type have been seen as the most important factors in predicting the prognosis and as a guide to plan treatment[2].However,patients with the same tumor type and stage of disease can show marked differences in prognosis.In patients undergoing complete surgical resection of pathologic stage IA NSCLC, approximately 10% of patients have a recurrence of the tumor and have a poor prognosis within one year[3-5]. So, additional tumor markers or identification of histopathological features is needed to better assess the survival probability and aid in identifying additional treatment modalities in stage I disease.Tumor angiogenesis is a requirement for solid tumor growth and metastasis. VEGF,known as vascular permeability factor,play a key role in tumor angiogenesis. Using immunohistochemical techniques and multivariate analyses we investigated the prognostic value of VEGF expression in stage IANSCLC and the prognostic importance of the relationship between VEGF expression and the clinical pathological features of stage IA NSCLC.Methods: Forty-nine patients undergoing complete surgical resection of pathologic stage IA NSCLC (International Union Against Cancer: TNM Classification of Malignant Tumors, 1997).were evaluated,involing a total of 183 hilar and mediastinal LNs. Paraffin-embedded tumor specimens were stained with VEGF. VEGF staining was evaluated, by combining both percentage of positive tumor cells and staining intensity, as low (negative and < 20% of tumor cells showing weak positivity), or high (≥20% of tumor cells showing strong positivity).The associations between the clinicopathologic characteristics and VEGF expresson were analyzed. Statistical significance was evaluated using the X2 test. A univariate survival analysis for each prognostic variable on overall survival was estimated according to the Kaplan-Meier method. The Cox proportional hazards model was applied to the multivariate survival analysis.Results: Low VEGF expression was seen in 25 (51.22%) patients, and high VEGF expression was seen in 24 (48.78%) patients. High VEGF expression in LNs was detected in 3 (6.12%)of 49 patients. High VEGF expression of primary tumor is correlated with tumor type and differentiation.The survival rate in primary tumor of patients with low VEGF expression was higher (76%) than that in those with high VEGF expression (55%),but nonsignificantly . High VEGF expression in LNs as a independent factor predicting worsening prognosis using multivariate analysis(p=0.09).Age, sex, tumor type, and tumor differentiation were not found to be associated with overall survival.Conclusion: VEGF expression rate of stage IA NSCLC primary tumor is high and correlated with tumor type and differentiation.High VEGF expression in LNs within stage IA NSCLC is an independent factor to judge patients' prognosis.The detection of lymph nodal VEGF expression can provide an powerful prognostic implications for completely resected stage IA NSCLC patients.