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

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.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.Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.The major cause of death from malignant tumors including non-small cell lung cancer (NSCLC) is dissemination of the primary tumor, leading to formation of metastases. Spread to regional lymph nodes is often the first step of generalization. Thus, the presence of lymph node metastasis represents a major criterion for evaluating the prognosis of NSCLC patients. Tumor-associated lymphangiogenesis are considered as the main route for lymphatic metastasis. And lymphovascular invasion (LVI) of tumor cells is a prerequisite for the dissemination via the lymphatic system. However, Studies of lymphatic vessels and lymphogenic metastasis have been hampered by the lack of specific lymphatic markers. Recently several markers for normal and tumor-associated lymphatic vessels have provided tools f