Smoller B A, McNutt N S, Carter D M, Gottlieb A B, Hsu A, Krueger J
Department of Pathology and Medicine, Cornell University Medical Center-New York Hospital, NY 10021.
Arch Dermatol. 1990 Jan;126(1):78-83.
Epidermolysis bullosa represents a grouping of inherited skin diseases characterized by epidermal fragility and frequently wounded skin. The recessive dystrophic subtype of epidermolysis bullosa (RDEB) is characterized by extensive dermal scarring after healing of repeated epidermal injuries and by an unusually high incidence of squamous cell carcinoma occurring in chronically wounded skin. In contrast, the simplex form of epidermolysis bullosa usually heals without scarring and does not predispose to malignant neoplasms of the skin. The differences in scarring and the neoplastic potential of these two forms of epidermolysis bullosa prompted us to investigate growth activation and differentiation characteristics in epidermal keratinocytes in individuals with these disorders. The expression of filaggrin, involucrin, cytokeratins, and the growth activation marker psi-3 was examined by immunohistochemistry in skin biopsy specimens from four individuals with epidermolysis bullosa simplex and six individuals with RDEB. Previous experiments using this technique have demonstrated that these antibodies are good markers for identifying growth-activated keratinocytes in wounded and hyperplastic epidermis. All biopsy specimens of healed wounds in skin from patients with RDEB showed epidermis that reacted with antibodies to filaggrin, involucrin, specific cytokeratins, and psi-3 in a growth-activated pattern. This growth-activated phenotype was maintained in keratinocytes from previously wounded skin that had been healed for more than 2 years. The RDEB growth-activated phenotype detected by immunohistochemistry was not associated with microscopically detectable epidermal hyperplasia. In contrast, all cases of epidermolysis bullosa simplex examined showed an epidermal phenotype similar to that of keratinocytes in normal skin. Thus, healing with dermal scar formation in RDEB is associated with a persistent growth-activated immunophenotype of epidermal keratinocytes. This chronic growth activation state or failure of cells to differentiate in a normal fashion may be directly linked to the high incidence of squamous cell cancers in individuals with RDEB.
大疱性表皮松解症是一组遗传性皮肤病，其特征为表皮脆弱且皮肤经常受伤。隐性营养不良型大疱性表皮松解症（RDEB）的特点是反复表皮损伤愈合后出现广泛的真皮瘢痕形成，以及慢性受伤皮肤中鳞状细胞癌的发病率异常高。相比之下，单纯型大疱性表皮松解症通常愈合后无瘢痕形成，且不易发生皮肤恶性肿瘤。这两种类型的大疱性表皮松解症在瘢痕形成和肿瘤发生潜能方面的差异促使我们研究患有这些疾病的个体表皮角质形成细胞的生长激活和分化特征。通过免疫组织化学检测了来自4例单纯型大疱性表皮松解症患者和6例RDEB患者的皮肤活检标本中丝聚蛋白、兜甲蛋白、细胞角蛋白和生长激活标志物psi-3的表达。此前使用该技术的实验表明，这些抗体是识别受伤和增生性表皮中生长激活的角质形成细胞的良好标志物。RDEB患者皮肤愈合伤口的所有活检标本均显示表皮以生长激活模式与抗丝聚蛋白、兜甲蛋白、特异性细胞角蛋白和psi-3的抗体发生反应。这种生长激活表型在先前受伤且已愈合超过2年的皮肤的角质形成细胞中得以维持。免疫组织化学检测到的RDEB生长激活表型与显微镜下可检测到的表皮增生无关。相比之下，所有检测的单纯型大疱性表皮松解症病例均显示出与正常皮肤角质形成细胞相似的表皮表型。因此，RDEB中伴有真皮瘢痕形成的愈合与表皮角质形成细胞持续的生长激活免疫表型相关。这种慢性生长激活状态或细胞未能以正常方式分化可能与RDEB患者中鳞状细胞癌的高发病率直接相关。
