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VEGF, MVD, and metastases in
gastric carcinoma

The association of high MVD with the presence of metastases was examined by Tanigawa et al using specimens from 110 patients who had curative gastrectomy from 1983 to 1993. No patients received preoperative chemotherapy or radiotherapy. They found that, as vessel counts increased, the incidence of hematogenous metasases increased. High MVD has been found to predict an increased risk of metastases, and the study by Tanigawa et al extended these findings to gastric carcinomas.¹

Tanigawa et al found that the vessel counts for hematogenous metastatic tumors were significantly higher than those for nonmetastatic tumors (P<0.00001). Vessel counts were also significantly higher than those for peritoneal metastatic tumors (P<0.01).¹

Higher microvessel count was associated with increased
hematogenous metastasis¹

Correlation of hematogenous metastasis and vessel count in 107 patients. The study included 67 male and 40 female participants with an average age of 63 years. Numbers above columns correspond to number of patients with metastases out of total patients in each column.

Reprinted with permission from Tanigawa N, Amaya H, Matsumura M, et al. Cancer Res. 1996;56:2671-2676. Figure 2B.

VEGF and prognosis in gastric cancer

The expression of VEGF has been associated with vascular invasion, liver metastases, and lymph node metastases. Fondevila et al examined MVD, VEGF expression, and p53 expression as independent prognostic factors for patients undergoing curative gastrectomy.²

VEGF influences overall survival time and disease-free survival time²

VEGF levels exerted significant effects on overall survival (A) and disease-free survival (B) in gastric cancer patients (N=156) (P<0.02).

Reprinted with permission from Fondevila C, Metges JP, Fuster J, et al. Br J Cancer. 2004;90:206-215. Figure 4.

The study utilized tissue samples from 156 patients with primary gastric cancer who underwent curative resection during a 9-year period. Immunohistochemical analyses were conducted using the automated immunohistochemical system.² The mean follow-up time was 43 months (95% CI, 37–49 months). VEGF expression was detected in 116 (74%) patients.²

The principal findings were as follows²:

• VEGF expression was associated with shorter overall survival time in patients with VEGF-positive vs VEGF-negative tumors (HR=2.48 [95% CI, 1.16–5.28], P=0.02)
• Disease-free survival time was also diminished in patients with VEGF-positive tumors
• VEGF expression was significantly correlated with MVD ≥100 mean number of vessels per x250 field of view (odds ratio [OR]=2.65 [95% CI, 1.33–5.29], P=0.005)
• High MVD levels were associated with shorter disease-free survival times
• MVD ≥100 was found to be significantly associated with lymph node metastases (P<0.003)
• In a univariate analysis, VEGF expression and tumor MVD were each independently and significantly associated with tumor recurrence and disease-free survival

MVD and prognosis in gastric cancer

Angiogenesis plays a central role in cancer cell survival, local tumor growth, and the development of distant metastases. The degree of microvessel density (MVD) influences tumor metastasis and, consequently, prognosis in gastric cancer.³

A significant correlation between MVD and disease-specific survival was seen in the study by Zhao et al. They analyzed specimens from 67 radical gastrectomies performed between 1997 and 2000. Patients with prior chemotherapy or radiotherapy were excluded. Mean follow-up time was 34 months (range 16 days to 60 months).³

High MVD was significantly associated with poor survival compared with low MVD (P<0.001). Sixty-seven patients (54 men and 13 women with a median age of 56 years) that underwent radical gastrectomy were enrolled into the study.³

Adapted from Zhao HC, Qin R, Chen XX, et al. World J Gastroenterol. 2006;12:7598-7603. Figure 1.

By multivariate survival analysis, MVD was judged to be an independent prognostic factor for survival in gastric carcinoma, as was lymph node metastasis.³ A significant difference in the overall survival rate was found between patients according to the MVD value (P<0.001), and comparison between low and high MVD.³

References:

1.

Tanigawa N, Amaya H, Matsumura M, et al. Cancer Res. 1996;56:2671-2676.

2.

Fondevila C, Metges JP, Fuster J, et al. Br J Cancer. 2004;90:206-215.

3.

Zhao HC, Qin R, Chen XX, et al. World J Gastroenterol. 2006;12:7598-7603.