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).


METHODS
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.


CONCLUSIONS
Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.
Sun
Jian-guo
JG
Cancer Institute of People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, PR China. sunjianguo1972@yahoo.com.cn
Wang
Yan
Y
Chen
Zheng-tang
ZT
Zhuo
Wen-lei
WL
Zhu
Bo
B
Liao
Rong-xia
RX
Zhang
Shao-xiang
SX
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; D033921:Vesicular Transport Proteins; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin