CELLULAR MARKERS THAT DISTINGUISH THE PHASES OF HEMANGIOMA DURING INFANCY AND CHILDHOOD
CELLULAR MARKERS THAT DISTINGUISH THE PHASES OF HEMANGIOMA DURING INFANCY AND CHILDHOOD
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DOI：
10.1172/jci117241
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发表时间：
1994-06-01
影响因子：
15.9
通讯作者：
EZEKOWITZ, RAB
中科院分区：
文献类型：
--
作者：
TAKAHASHI, K;MULLIKEN, JB;EZEKOWITZ, RAB
血管瘤，局部肿瘤的血管，出现在类似的10-12%的白人婴儿。这些病变的特征是第一年毛细血管快速增殖（增殖期），随后在随后的1-5年内缓慢、不可避免地消退（消退期），并持续改善直至6-12岁（消退期）。为了在细胞水平上描绘血管瘤的临床观察生长阶段，我们使用9种独立的标记物进行了免疫组化分析。增殖期由增殖细胞核抗原、IV型胶原酶和血管内皮生长因子的高表达定义。金属蛋白酶组织抑制剂TIMP 1（一种新血管形成的抑制剂）的表达升高仅在退化期观察到。碱性成纤维细胞生长因子（bFGF）和尿激酶在增殖期和退化期呈高表达。增殖期bFGF与内皮细胞表型标志物CD 31和von Willebrand因子共表达。这些结果提供了一个客观的基础分期血管瘤，并可用于评估药物，如皮质类固醇和干扰素α-2a，加速血管瘤的消退。相反，血管畸形不表达增殖细胞核抗原、血管内皮生长因子、bFGF、IV型胶原酶和尿激酶。这些数据表明增殖性血管瘤和血管畸形之间的免疫组化差异，反映了这些血管病变之间的生物学差异。
Hemangiomas, localized tumors of blood vessels, appear in similar to 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.