Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

Background: Our aim was to detect lymphatic endothelial marker podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and vascular endothelial growth factor receptor-3 (VEGFR)-3 and study the prognostic relevance of lymphangiogenesis in non-small cell lung cancer (NSCLC). Materials: 82 paraffin-embedded tissues and 40 fresh frozen tissues from patients with NSCLC were studied. Tumor samples were immunostained for the lymphatic endothelial markers. Lymphangiogenesis was assessed by immunohistochemical double stains for Podoplanin and Ki-67. The prognostic relevance of lymphangiogenesis-related clinicopathological parameters in NSCLC was evaluated. Results: We found that the number of podoplanin positive vessels was correlated positively with the number of LYVE-1 positive vessels. Most of VEGFR-3 positive, few of LYVE-1 positive and none of podoplanin positive vessels were blood vessels. Peritumoral lymphatic vessel density (ptLVD), pathologic stage, lymph node status, lymphatic vessel invasion (LVI), vascular endothelial growth factor-C (VEGF-C) expression and Ki-67 index of the endothelium cells of the micro lymphatic vessels (Ki67%) were associated significantly with a higher risk of tumor progress. ptLVD, pathologic stage, lymph-node metastasis and Ki67% were independent prognostic parameters for overall survival. Conclusion: Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.