[Expression of vascular endothelial growth factors (VEGF)-A, -C and -D and their prognostic significance and relationship with angio- and lymphangiogenesis in gastric cancer].
OBJECTIVE
To investigate the expressions of vascular endothelial growth factors (VEGF)-A, -C and -D and their prognostic significance and relation to angio- and lymphangiogenesis in gastric cancer.


METHODS
The expression of VEGF-A, -C and -D in 123 primary gastric cancers was detected by immunohistochemical staining. The lymphatic vessel density (LVD) and microvessel density (MVD) were assessed after immunohistochemical double-staining with D2-40 and CD34, respectively. The correlation between the expression of those VEGF factors and clinicopathological parameters were analyzed by univariate method. The overall survival was evaluated by Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using Cox proportion hazard model.


RESULTS
The positive expression rate of VEGF-A, -C and -D in primary gastric cancer samples were 64.2%, 65.9% and 41.5%, respectively. High expression of VEGF-A, or -C or -D, or any two of them was correlated with high LVD (P < 0.05). High expression of both VEGF-A and -C was associated with high MVD, lymph node metastasis, LVI and MVI (P < 0.05). Both VEGF-C and -D high expression was correlated with LVI and lymph node metastasis (P < 0.05). The patients with high expression of these factors had a statistically shorter overall survival (P < 0.05). The patients with both VEGF-A and -C expression had the shortest survival (56 months). Multivariate analysis showed that VEGF-A high expression, MVD, lymph node metastasis and depth of tumor invasion were independent survival predictors (P = 0.033, 0.002, 0.019 and P < 0.001, respectively).


CONCLUSIONS
High expression of both VEGF-A and -C imply high potential of lymphangiogenesis, metastasis and poorer survival in gastric cancer patients. High expression of VEGF-C and -D may induce lymphangiogenesis and promote lymph node metastasis, but only VEGF-A is an independent predictor of survival.
Wang
Xiao-lei
XL
Department of Gastroenternology, Tongji Hospital, Tongji University, Shanghai 200065, China. xlwang2006@163.com
Ai
Zi-sheng
ZS
Fang
Jian-ping
JP
Tang
Ru-yong
RY
Chen
Xi-mei
XM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D