Abstract
In radically resected gastric cancer the possibility to predict the site of relapse could be clinically relevant for the selection of post-surgical management. We previously showed that specific tumour integrins genotypes are independently associated with either peritoneal or hematogenous metastases (ITGA and ITGV). Recently VEGF and VEGF-R polymorphisms have been demonstrated to potentially affect tumour angiogenesis and the metastatic process in gastric cancer. We then investigated the role of VEGFs and VEGF-R genotyping in determining either peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer patients. Tumour genotyping for integrins (ITGA and ITGV) was also performed according to our previous findings. Genotyping for VEGF-A, VEGF-C, VEGFR-1,2,3 and ITGA and ITGV was carried out on pT4a radically resected gastric tumours recurring with either peritoneal-only carcinosis or hematogenous metastases. 101 patients fulfilled the inclusion criteria: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. At multivariate analysis, intestinal histology and the AC genotype of rs699947 (VEGFA) showed to independently correlate with hematogenous metastases (p = 0.0008 and 0.008 respectively), whereas diffuse histology and the AA genotype of rs2269772 (ITGA) independently correlated with peritoneal-only diffusion (p = <0.0001 and 0.03 respectively). Our results seem to indicate that combining information from genotyping of rs699947 (VEGFA, AC), rs2269772 (ITGA, AA) and tumour histology could allow clinicians to individuate gastric cancer at high risk for recurrence either with peritoneal or hematogenous metastases. The selection tool deriving from this analysis may allow an optimal use of the available treatment strategies in these patients.
Highlights
The global outcome for radically resected gastric cancer patients remained substantially unchanged across the years in western Countries, with a 5-years survival rate ranging between 15% and 35% of all cases [1,2]
We investigated the role of Vascular Endothelial Growth Factor (VEGF) and VEGF receptors (VEGF-R) genotyping in determining either peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer patients
In a previous analysis we found that Genotyping of rs2269772 (ITGA) and rs11902171 (ITGV) may represent a critical asset in the definition of high risk gastric cancer patients for peritoneal carcinosis [10]
Summary
The global outcome for radically resected gastric cancer patients remained substantially unchanged across the years in western Countries, with a 5-years survival rate ranging between 15% and 35% of all cases [1,2]. Peritoneal carcinosis may be the first site of relapse in approximately 40 to 50% of patients undergoing radical resection [5,6,7]. Based on these data a potential role for intraperitoneal chemotherapy in the prevention of peritoneal carcinomatosis has been hypothesized [6,7]. Clinical and pathological factors such as tumour serosal involvement, tumour histology (diffuse vs intestinal), the extent of lymphadenectomy and the presence of tumour cell in peritoneal lavage during laparotomy have been indicated as predictive for the site of recurrence in gastric cancer [4,8,9]
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