Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients

• Published in: Human pathology Vol. 41; no. 5; pp. 737 - 744
• Main Authors: Chen, Zhenguang, MD, PhD, Wang, Tao, PhD, Luo, Honghe, MD, Lai, Yingrong, Yang, Xuhui, PhD, Li, Fugui, MD, Lei, Yiyan, MD, Su, Chunhua, MD, PhD, Zhang, Xiuming, Lahn, Bruce T., PhD, Xiang, Andy Peng, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2010; Elsevier; Elsevier Limited
• Subjects: Aged; Antigens, CD34 - metabolism; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Classification; Cyclooxygenase 2 - metabolism; Female; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Intermediate Filament Proteins - metabolism; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymph node metastases; Lymphangiogenesis; Lymphangiogenesis - physiology; Lymphatic Metastasis; Lymphatic system; Lymphatic Vessels - metabolism; Lymphatic Vessels - pathology; Male; Medical sciences; Middle Aged; Mortality; Multivariate analysis; Neoplasm Staging; Nerve Tissue Proteins - metabolism; Nestin; Non-small cell lung cancer; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pneumology; Prognosis; Regression Analysis; Statistics, Nonparametric; Thoracic surgery; Tumors; Tumors of the respiratory system and mediastinum; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-3 - metabolism; Nestin; Lymph node metastases; Lymphangiogenesis; Non-small cell lung cancer; Human; Lung disease; Respiratory disease; Lung cancer; Malignant lymphadenopathy; Malignant hemopathy; Malignant tumor; non-small cell lung carcinoma; Lymph node metastasis; Anatomic pathology; Bronchus disease; Cancer
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2009.10.018

Summary 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.