Basic fibroblast growth factor receptors and their prognostic value in human breast cancer

We performed a saturation binding study with (125)I(_)labeled FGF (fibrobla st growth factor)-2 in a nonselected series of 250 human primary breast can cers, Two hundred twenty-five breast cancer biopsies possessed bFGFR (basic FGF receptor). The median dissociation constant was 0.35 nra (range, 0.014 -1.9), and the median concentration was 1126 fmol/mg protein (range, 49-732 8). FGFR-1 was localized, using a specific monoclonal antibody, in cancerous ce lls and in epithelial cells in normal breast or in benign tumors. In all of the tissues studied, light stromal cell staining was also observed. Thus, the localization of FGFR-1 in carcinoma cells supports the hypothesis that an important part of FGF-2 binding reflects binding to FGFR-1, bFGFR concentrations were positively correlated to estrogen receptor and pr ogesterone receptor levels. Cox univariate analyses showed that the bFGFR ( greater than or equal to upper quartile) was associated to longer relapse-f ree survival [P = 0.004; RR (risk ratio), 0.46] and overall survival (P = 0 .001; RR, 0.35); age, estrogen receptor levels, progesterone receptor level s, node involvement, tumor diameter, and histoprognostic grading were progn ostic, also, In Cox multivariate analyses, only the bFGFR, age, node involv ement, and histoprognostic grading were prognostic factors; the bFGFR was a ssociated with longer relapse-free survival (P = 0.03; RR, 0.4) and overall survival (P = 0.009; RR, 0.3), The present study confirms that FGF could be an important regulator of huma n breast cancer growth and that patients with a high level of bFGFR had a b etter prognosis.