Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease

BACKGROUND. Clinical data clearly indicate a correlation between tumor neov ascularization, aggressiveness of tumor growth, and metastatic spread. One of the key factors capable of stimulating tumor angiogenesis is vascular en dothelial growth factor (VEGF). Using an immunoassay for VEGF, we assessed the levels of soluble VEGF in the sera and effusions of patients with malig nant and nonmalignant disease as well as in the sera of healthy controls. METHODS. Using a sandwich enzyme-linked immunoadsorbent assay, the concentr ation of VEGF was measured in serum specimens (n = 445) and effusions (n = 56) collected from a total of 212 patients with various types of cancer, 88 patients with nonmalignant disease, and 145 healthy individuals. RESULTS. Low and rather stable levels of VEGF were detected in the serum of healthy individuals (median, 294 pg/mL; range, 30-1752 pg/mL; 95th percent ile, 883 pg/mL). Compared with healthy individuals, serum levels in patient s with acute infections were elevated (P = 0.03), whereas patients with chr onic cirrhosis had lower serum VEGF levels. Among patients with various typ es of neoplasia, VEGF serum levels in patients with ovarian or gastrointest inal carcinoma were significantly higher than in healthy individuals. Moreo ver, VEGF concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum con centrations of VEGF (median, 1022 pg/mL; range, 349-7821 pg/mL) were found in patients with metastatic ovarian carcinoma. Median VEGF levels (and rang es) in malignant effusions were up to 10-fold higher than in matched serum samples: 5528 pg/mL (468-49269 pg/mL) in ovarian carcinoma, 885 pg/mL (77-1 4,337 pg/mL) in breast carcinoma, and 813 pg/mL (372-18,331 pg/mL) in gastr ointestinal. carcinoma. In contrast, ascitic fluid from patients with cirrh osis contained only 303 pg/mL (median, range 116-676 pg/mL) of VEGF, corres ponding to the low serum levels in this patient group. CONCLUSIONS. Depending on the tumor type, elevated levels of VEGF are detec table in the serum of only 0-20% of patients with localized cancer but in 1 1-65% of patients with metastatic cancer. Of cytology-proven malignant asci tes or peritoneal exudates from various malignancies, 46-96%, show VEGF lev els above the upper limit (95th percentile, 676 pg/mL) of nonmalignant asci tes. Maximum VEGF concentrations in malignant effusions indicate abundant l ocal release of VEGF within the pleural or peritoneal cavity. These results suggest that VEGF might play an important role in tumor progression and th e formation of malignant effusions. Further studies are warranted to determ ine the clinical value of soluble VEGF as a tumor marker, a prognostic fact or, and a surrogate indicator of tumor angiogenesis. Cancer 1999;85:178-87. (C) 1999 American Cancer Society.