Lymphatic microvessel density as a prognostic factor in non-small cell lung carcinoma: a meta-analysis of the literature
OBJECTIVE The aim of this study was to investigate the clinical and prognostic significance of lymphangiogenesis in non-small cell lung carcinoma (NSCLC). METHODS The expression of lymphatic vessel endothelium markers podoplanin, VEGFR-3 and vascular endothelium marker CD31 was detected in paraffin sections from 68 cases of NSCLC and 8 cases of pulmonary inflammatory myofibroblastic tumor (PIMT) by immunohistochemistry (SP). Microvessel density (MVD) and lymphatic vessel density (LVD) were counted. Specificity of lymphatic vessel endothelium markers was compared between VEGFR-3 and podoplanin. Lymphangiogenesis, quantified by evaluating LVD, was correlated with various clinical pathological parameters and prognostic relevance. RESULTS No significant association was found between the number of podoplanin positive vessels and the number of CD31 positive or VEGFR-3 positive vessels (r = -0.171, P = 0.124; r = 0.003, P = 0.979), but the counts of VEGFR-3 positive vessels were associated with CD31 positive vessel counts (r = 0.331, P = 0.002). LVD in PIMT group was significantly lower than that in NSCLC group (P = 0.004). Compared with that without the lymph node metastasis group, LVD in the positive group increased significantly (P = 0.033); LVD in pathological stage III and IV was higher than that in pathological stage I and II (P = 0.001). There was no difference of LVD in different cell differentiation, age and sex groups. The 5-year survival rate for high LVD was significantly lower than that of low LVD. Multivariate analysis showed that LVD was a significant and independent prognostic factor. CONCLUSIONS Lymphangiogenesis may be a significant prognostic factor for NSCLC.