Tumor angiogenesis as predictive factor for site of relapse in patients with gastric cancer: Biological and clinical implications.

Abstract

e21119 Background: Tumor integrins are relevant for gastric cancer diffusion. Preclinical studies suggested that angiogenesis is also crucial for metastatic spread. We investigated the role of VEGF and VEGF-R genotyping and integrin polymorphisms in determining either peritoneal or hematogenous metastases in radically resected gastric cancer. Methods: Genotyping for VEGF-A, VEGF-C and VEGFR-1,2,3 and for tumor integrins was carried out on pT3, peritoneal washing negative, radically resected gastric cancer patients recurring with either peritoneal-only or hematogenous metastases. Results: 101 patients were analyzed: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. The following VEGF polymorphisms were associated with hematogenous metastases at the univariate analysis: the AA genotype of rs1570360 (VEGF-A) (p=0.0282), the AC genotype of rs699947 (VEGF-A) (p=0.006) and the GG genotype of rs7993418 (VEGFR-1) (p=0.0259). The following tumoral integrin polymorphisms were associated with hematogenous metastases at univariate analysis: the GG genotype of rs2269772 (ITGA3) (p=0.0002) and the GG genotype of rs11902171 (ITGV) (p=0.029). An increased rate of peritoneal carcinomatosis was found with the AA genotype of ITGA3 (p=0.014) and the CC genotype of ITGV (p=0.016). Variables with a statistically significant odds ratio for peritoneal carcinomatosis at the multivariate analyisis were diffuse tumoral histology (OR: 43,35, 95% CI: 9.07-207.9, p<0.0001) and the AA genotype of ITGA3 (OR: 5.69, 95% CI: 1.1-29.9, p=0.04). At the multivariate analysis the AC genotype of VEGF-A (OR: 8.08, 95% CI: 1.7-37.5, p=0.008) and intestinal histology (OR: 4.2, 95% CI: 1.8-9.9, p=0.0008) were independently associated with hematogenous metastases Conclusions: Tumor histology still represents a crucial factor for site of relapse. Furthermore a specific integrin polymorphism (AA genotype of ITGA3) and a specific VEGF-A polymorphism (AC genotype of VEGF-A) may represent a further asset in the definition of high-risk patients for respectively peritoneal carcinomatosis or hematogenous relapse.