Arbiser J L, Fine J D, Murrell D, Paller A, Connors S, Keough K, Marsh E, Folkman J
Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
Mol Med. 1998 Mar;4(3):191-5.
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 squamous cell carcinoma. Patients with other genetic blistering disorders do not have elevated collagenase or an increased risk of squamous cell carcinoma, despite chronic wounding. The connection between collagen type VII deficiency, increased collagenase, and squamous cell carcinoma is not understood.
Urine from 81 patients with RDEB (39 patients), junctional epidermolysis bullosa (JEB; 12 patients), and epidermolysis bullosa simplex (EBS; 30 patients), as well as unaffected family members of RDEB patients (33 patients), was tested for the presence of basic fibroblast growth factor (bFGF) using a sensitive radioimmunoassay. These patients included many who were enrolled in the Epidermolysis Bullosa Registry and others who were referred by their physicians.
Fifty-one percent of patients with RDEB had elevated levels (> 5000 pg/g) of urinary bFGF. In contrast, none of the patients with JEB had elevated levels of bFGF. Twenty-one percent of clinically unaffected family members had elevated levels of bFGF, and 13% of patients with EBS had elevated levels of bFGF. The frequency of elevated bFGF values among all groups was statistically significant (p = 0.002), and the levels of bFGF in RDEB patients were significantly elevated compared with those of other groups (p < 0.05).
We have found that patients with RDEB have elevated levels of bFGF, which may contribute to increased fibroblast collagenase and the development of squamous cell carcinoma. These results suggest a novel treatment for RDEB, namely, angiogenesis inhibitors, which may antagonize the effects of bFGF in this disorder. There are currently no other means of treatment for this disorder, which has a high morbidity and mortality rate.
隐性营养不良性大疱性表皮松解症（RDEB）患者存在Ⅶ型胶原蛋白缺乏，成纤维细胞胶原酶水平升高，患皮肤鳞状细胞癌的风险大幅增加。其他遗传性水疱病患者尽管有慢性伤口，但胶原酶水平未升高，患鳞状细胞癌的风险也未增加。Ⅶ型胶原蛋白缺乏、胶原酶增加与鳞状细胞癌之间的联系尚不清楚。
使用灵敏的放射免疫分析法检测了81例RDEB患者（39例）、交界性大疱性表皮松解症（JEB；12例）和单纯性大疱性表皮松解症（EBS；30例）患者以及RDEB患者未受影响的家庭成员（33例）尿液中碱性成纤维细胞生长因子（bFGF）的存在情况。这些患者包括许多登记在大疱性表皮松解症登记处的患者以及其他经医生转诊的患者。
51%的RDEB患者尿bFGF水平升高（>5000 pg/g）。相比之下，JEB患者中无一例bFGF水平升高。21%临床未受影响的家庭成员bFGF水平升高，13%的EBS患者bFGF水平升高。所有组中bFGF值升高的频率具有统计学意义（p = 0.002），RDEB患者的bFGF水平与其他组相比显著升高（p < 0.05）。
我们发现RDEB患者的bFGF水平升高，这可能导致成纤维细胞胶原酶增加和鳞状细胞癌的发生。这些结果提示了一种针对RDEB的新治疗方法，即血管生成抑制剂，其可能拮抗bFGF在该疾病中的作用。目前对于这种发病率和死亡率高的疾病没有其他治疗方法。
