VEGF is a target molecule for peritoneal metastasis and malignant ascites in gastric cancer: prognostic significance of VEGF in ascites and efficacy of anti-VEGF monoclonal antibody

Abstract

Sachio Fushida, Katsunobu Oyama, Jun Kinoshita, Yasumichi Yagi, Kouichi Okamoto, Hidehiro Tajima, Itasu Ninomiya, Takashi Fujimura, Tetsuo OhtaDepartment of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, JapanBackground: In gastric cancer, poor prognosis is associated with peritoneal dissemination, which often accompanies malignant ascites. We searched for a target molecule in peritoneal metastasis and investigated its clinical utility as a biomarker.Methods: Biopsy specimens from both primary lesions and peritoneal metastasis, and if possible, malignant ascites, were obtained from 40 patients with gastric cancer. Vascular endothelial growth factor (VEGF) expression was analyzed by immunohistochemical staining and enzyme-linked immunosorbent assay.Results: VEGF expression was seen in 70% of peritoneal samples. Of the 40 patients, 35 had malignant ascites. These 35 patients were divided into two groups: 15 with ascites found beyond the pelvic cavity (large group) and 20 whose ascites were within the pelvic cavity (small group). The two groups did not significantly differ by serum VEGF levels, but ascites VEGF levels in the large group were significantly higher than in the small group (P < 0.0001). Serum VEGF and ascites VEGF levels were highly correlated in the large group (r = 0.686). A high ascites VEGF level was found to be a risk factor for survival (P = 0.045). We include a report of a patient with chemoresistant refractory gastric cancer and symptomatic ascites who obtained 8 months of palliation from systemic bevacizumab.Conclusion: Anti-VEGF therapies are promising, and the ascites VEGF level is an important marker in managing patients with gastric cancer and peritoneal metastasis.Keywords: vascular endothelial growth factor, malignant ascites, peritoneal metastasis, gastric cancer, bevacizumab