Abstract
BackgroundOur 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).Materials82 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.ResultsWe 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.ConclusionPodoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.
Highlights
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
A double immunostaining with the D2–40 and anti-Ki67 monoclonal antibody is used as the standard method for the assessment of lymphangiogenesis in solid tumors[17]
CD31, vascular endothelial growth factor receptor-3 (VEGFR-3), LYVE-1, VEGF-C Expression in NSCLC Numerous intratumoral and peritumoral vessels could be observed in each NSCLC tumor irrespective of histologic grade and pathologic stage
Summary
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. 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). Several markers for normal and tumor-associated lymphatic vessels have provided tools for a detailed analysis of lymphangiogenesis in human lung cancers These markers include vascular endothelial growth factor C and D (VEGF-C, VEGF-D) [1,2], vascular endothelial growth factor receptor-3 (VEGFR-3) [3,4,5,6], the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) [7] and glomerular podocyte membrane mucoprotein podoplanin [8]. The aim of this study was to detect Lymphangiogenesis and find the relationship between clinicopathological parameters, such as LVD, lymph-node metastasis, VEGFC, LVI, pathological stage, and prognostic factor in NSCLC
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