BASIC FIBROBLAST GROWTH-FACTOR - A MISSING LINK BETWEEN COLLAGEN-VII,INCREASED COLLAGENASE, AND SQUAMOUS-CELL CARCINOMA IN RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA

Background: Patients with recessive dystrophic epidermolysis bullosa ( RDEB) have deficiencies of collagen type VII and have elevated levels of fibroblast collagenase, and a greatly increased risk of cutaneous s quamous cell carcinoma. Patients with other genetic blistering disorde rs do not have elevated collagenase or an increased risk of squamous c ell carcinoma, despite chronic wounding. The connection between collag en type VII deficiency, increased collagenase, and squamous cell carci noma is not understood. Materials and Methods: Urine from 81 patients with RDEB (39 patients), junctional epidermolysis bullosa (JEB; 12 pat ients), and epidermolysis bullosa simplex (EBS; 30 patients), as well as unaffected family members of RDEB patients (33 patients), was teste d for the presence of basic fibroblast growth factor (bFGF) using a se nsitive radioimmunoassay. These patients included many who were enroll ed in the Epidermolysis Bullosa Registry and others who were referred by their physicians. Results: Fifty-one percent of patients with RDEB had elevated levels (>5000 pg/g) of urinary bFGF. Ln con trast, none o f the patients with JEB had elevated levels of bFGF. Twenty-one percen t of clinically unaffected family members had elevated levels of bFGF, and 13% of patients with EBS had elevated levels of bFGF. The frequen cy of elevated bFGF values among all groups was statistically signific ant (p = 0.002), and the levels of bFGF in RDEB patients were signific antly elevated compared with those of other groups (p < 0.05). Conclus ions: We have found that patients with RDEB have elevated levels of bF GF, which may contribute to increased fibroblast collagenase and the d evelopment of squamous cell carcinoma. These results suggest a novel t reatment for RDEB, namely, angiogenesis inhibitors, which may antagoni ze the effects of bFGF in this disorder. There are currently no other means of treatment for this disorder, which has a high morbidity and m ortality rate.