ELEVATED LEVELS OF THE ANGIOGENIC CYTOKINES BASIC FIBROBLAST GROWTH-FACTOR AND VASCULAR ENDOTHELIAL GROWTH-FACTOR IN SERA OF CANCER-PATIENTS

The concentration of basic fibroblast growth factor (bFGF) and vascula r endothelial growth factor (VEGF) was determined in the serum of 90 u ntreated and 42 treated metastatic cancer patients, including patients with colorectal, breast, ovarian and renal carcinomas, with an enzyme -linked immunosorbent assay (ELISA). Levels higher than the 95th perce ntile of the concentrations of a control group, i.e. 7.5 pg ml(-1) for bFGF and 500 pg ml(-1) for VEGF, were identified as 'elevated'. One m easurement during follow-up was included into the analysis per patient . For 19 treated patients, consecutive serum samples were analysed. Fi fty-seven per cent of all untreated patients had elevated serum levels of one or both angiogenic factors. The fraction of patients with elev ated serum levels of bFGF and/or VEGF was similar in the different tum our types. Agreement of bFGF levels and VEGF levels, classified in rel ation to their respective cut-off values, was present in 67% of all pa tients. Fifty-eight per cent of the patients with progressive disease during treatment compared with 15% of the patients showing response to treatment (chi-squared test P < 0.05) had elevated bFGF and/or VEGF s erum levels. When consecutive serum samples were analysed, two-thirds of the patients showing progressive disease had increasing serum level s of the angiogenic factors compared with less than one-tenth of the p atients showing response (chi-squared test P < 0.05). The lack of asso ciation between the serum bFGF and VEGF levels and the tumour type may suggest an aspecific host reaction responsible for solid tumour-relat ed angiogenesis. The main determinants of the serum bFGF and VEGF conc entration are the progression kinetics of the metastatic carcinomas.