Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients.
Stem cell marker nestin has been reported to be activated in various neoplasms, and its expression is correlated with poor prognosis. However, nestin expression in non-small cell lung cancer still remains unclear. The present study aimed to investigate nestin expression in 52 tissue samples of non-small cell lung cancer by immunohistochemical staining and explore its correlation with some clinicopathologic characteristics. The associations of nestin with lymphatic vessel density, microvessel density, vascular endothelial growth factor, vascular endothelial growth factor-C, and cyclooxygenase-2 (COX-2) were further observed to determine the linkage between nestin and lymphangiogenesis. The results showed that nestin expressed in tumor cells of 45 samples. High nestin expression correlated significantly with poor differentiation (P = .007), adenocarcinoma (P = .000), N2 lymph node metastasis (P = .006), high microvessel density (P = .033), and lymphatic vessel density (P = .020). Multivariate analysis of N1 and N2 lymph node metastasis revealed a 1.086-fold increase in hazard ratio of N2 lymph node involvement (P = .011) in patients with high nestin expression in primary tumor. More important, multivariate analysis showed a significant correlation of lymphatic vessel density with nestin and vascular endothelial growth factor-C expression (P = .039 and P = .045), independent of vascular endothelial growth factor, COX-2, and other clinicopathologic characteristics. The results demonstrated that nestin expressed in most tumor cells of non-small cell lung cancer tissue and had a direct linkage to lymph node metastasis and tumor-induced lymphangiogenesis, independent of COX-2 signal pathway.
Chen
Zhenguang
Z
Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
Wang
Tao
T
Luo
Honghe
H
Lai
Yingrong
Y
Yang
Xuhui
X
Li
Fugui
F
Lei
Yiyan
Y
Su
Chunhua
C
Zhang
Xiuming
X
Lahn
Bruce T
BT
Xiang
Andy Peng
AP
D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D011379:Prognosis; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D018952:Antigens, CD34; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D051546:Cyclooxygenase 2; D040321:Vascular Endothelial Growth Factor Receptor-3