Elevated Levels of an Angiogenic Peptide, Basic Fibroblast Growth Factor, in the Urine of Patients With a Wide Spectrum of Cancers

Abstract

BACKGROUND: Experimental evidence supports the hypothesis that the development of blood vessels is fundamental to the growth and metastasis of solid tumors. Elevated levels of the angiogenic peptide basic fibroblast growth factor (bFGF) have been significantly correlated with the status and extent of disease in bladder cancer. PURPOSE: We measured the bFGF levels in patients with cancer in organs other than the bladder to determine whether elevated levels accompany these cancers. METHODS: Urine samples were collected from 950 patients having a wide variety of solid tumors, leukemia, or lymphoma and from a control group of 87 healthy volunteers and 198 patients with non-cancer-related diseases. Levels of bFGF in samples prepared from the urine were measured using an enzyme bioassay. RESULTS: Male control subjects had a median bFGF level of 151 pg/g and female control subjects a median of 237 pg/g, with a combined 90th percentile of 619 pg/g. An elevated level of bFGF was found in the urine of some of the patients with every type of tumor studied except cervical carcinoma. For example, patients with active local cancers had a median level of 312 pg/g. Those with active, metastatic cancers had a median level of 479 pg/g and a 90th percentile level of 14143 pg/g. After "elevated" was defined to mean higher than the 90th percentile level for controls, 31% of patients with local active and 47% of patients with metastatic active cancers showed elevated bFGF levels. Survival among cancer patients at the median follow-up time was 85%-88% for those with "normal" and 71%-72% for those with "elevated" urine bFGF levels. IMPLICATIONS: Our results suggest that bFGF in urine deserves further evaluation of its potential use as a monitor of therapy or as a predictor of outcome once a cancer has been diagnosed.