Vascular Endothelial Growth Factor Staining Intensity Research Articles

Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma.

The relationship between the expression of vascular endothelial growth factor (VEGF) and its receptor, KDR, in human gastric carcinoma tissues and tumor angiogenesis, as well as patient outcome, were investigated. One hundred sixty-three primary tumor specimens were investigated by immunohistochemical studies with anti-VEGF, anti-KDR, and anti-CD34 antibodies and by monitoring patients for at least 2 years after surgery. For intensity of VEGF staining, 48 tumors were graded as 0, 36 as 1+, 63 as 2+, and 16 as 3+. Tumors with strong VEGF staining, assessed as 2+ and 3+, had significantly higher vascularity than those with weak VEGF. Eighty-eight tumors (54%) were positive for KDR. There was no association between KDR expression and tumor vascularity. No close correlation was found between VEGF and KDR expressions. The Cox proportional hazards model identified intratumoral vessel count as the most significant and independent prognostic factor among various clinicopathologic factors. In contrast, overall survival rates for 84 patients with weak VEGF staining tumors and 79 with strong VEGF staining tumors were not significantly different. Patients with tumors of either localized Borrmann types or well-differentiated histologies, which are found more frequently in tumors with strong VEGF staining, survived significantly longer than those with tumors of either infiltrative Borrmann types or poorly differentiated histologies. We suggest that expression of VEGF is more frequently found in tumors with well-differentiated histology and plays a role in the promotion of angiogenesis in human gastric carcinomas.

Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells.

Development of new blood vessels is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor and/or infiltrating cells. We previously showed that vascular endothelial growth factor (VEGF) expression and vessel count correlate with metastasis in human colon cancer. Although most tumors with high vessel counts express high levels of VEGF, some do not. Recently, platelet-derived endothelial cell growth factor (PD-ECGF), another potent angiogenic factor, has been reported to be expressed in colon cancer. In this study, we examined the role of PD-ECGF in colon cancer angiogenesis and whether PD-ECGF is derived from the tumor or infiltrating cells. Immunostaining for PD-ECGF was performed on 96 colon cancer specimens, some of which were previously stained for VEGF and factor VIII, a marker that is specific for endothelial cells. Double staining was done by using antibodies to PD-ECGF and to CD68 (macrophage specific) or CD3 (lymphocyte specific) to confirm which infiltrating cells produce PD-ECGF. Northern blot analysis for PD-ECGF messenger RNA (mRNA) was performed on four colon cancer specimens and corresponding normal colon mucosae (same patients) and four human colon cancer cell lines (KM12SM, SW620, HT29, and NCI-H508) to determine whether colon cancer epithelium expresses PD-ECGF. Immunohistochemical analysis demonstrated that PD-ECGF was expressed in infiltrating cells in most of the colon cancer specimens (80 [83%] of 96) but rarely in tumor epithelium (five [5%] of 96). Double staining demonstrated that infiltrating cells staining positive for both PD-ECGF and CD68 were more predominant than those staining positive for both PD-ECGF and CD3. The intensity of staining for PD-ECGF in infiltrating cells correlated with vessel counts (Spearman's rank correlation coefficient (R) = .29; P = .004), but did not correlate with the intensity of VEGF staining (R = .176, P = .086) or metastasis (Mann-Whitney U test, P = .253). PD-ECGF staining intensity was higher in specimens with a high vessel count (> 50 at high magnification) and low VEGF-staining intensity (< or = 2+) than in specimens with a high vessel count (again, > 50) and high VEGF-staining intensity (3+). Northern blot analysis revealed that colon cancer specimens and normal mucosae expressed relatively high levels of PD-ECGF mRNA, whereas PD-ECGF mRNA transcripts were not detectable in colon cancer cell lines. PD-ECGF expression in human colon cancer specimens is associated with vessel count and may be responsible for tumor vascularity in those tumors with low VEGF expression. Infiltrating cells expressing PD-ECGF may contribute to angiogenesis, thus providing an additional mechanism for tumor neovascularization.