title: Lymphangiogenesis in gastric carcinoma correlates with prognosis.
abstract: Lymphatic metastasis is an important way that gastric carcinomas can spread. However, little is known about the mechanisms of lymphangiogenesis and its clinical significance in gastric carcinomas. In the present study, lymphatic vessel density (LVD), VEGF-C expression, and proliferative activity of lymphatic endothelium were determined in human gastric carcinomas and xenografts of gastric cancer cells in nude mice. The development of lymphangiogenesis and its correlation with patient prognosis were investigated. The results showed that lymphatic vessels were observed mainly in peripheral tumour tissue with significantly (p < 0.05) higher P-LVD (peri-tumoural-LVD) than I-LVD (intra-tumoural-LVD). The expression of VEGF-C was heterogeneous within tumours, with a significantly higher expression (immunostaining score) at the margin than at the tumour centre (p < 0.05). A significant correlation was found between VEGF-C expression at the margin (but not at the centre) and P-LVD (r = 0.72, p < 0.01). High proliferative activity of lymphatic endothelium was also observed in the peripheral tissues, with a significant correlation between proliferative activity of lymphatic endothelium and VEGF-C expression (p < 0.05). These data imply that the increased lymphatics may have been newly formed following stimulation by VEGF-C. High VEGF-C expression at the margin of gastric carcinomas could induce lymphangiogenesis in the peri-tumoural stroma and contribute to the increased P-LVD. The data from mice tumour xenografts also suggested that VEGF-C produced from the transplanted gastric carcinoma cells could induce lymphangiogenesis around them. In patients, VEGF-C expression at tumour margins was associated with nodal metastasis, lymphatic vessel invasion, poor recurrence-free survival, and poor overall survival, and could serve as an independent predictor for patients with gastric carcinoma.
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, Jinan, PR China. gaopeng@sdu.edu.cn
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Geng-Yin
authors.initials: GY
authors.lastname: Zhou
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Zhang
authors.forename: Zhong-Xue
authors.initials: ZX
authors.lastname: Su
authors.forename: Ting-Guo
authors.initials: TG
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Xiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shun-Li
authors.initials: SL
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D042582:Vascular Endothelial Growth Factor C