Tan S T, Velickovic M, Ruger B M, Davis P F
Swee Tan Plastic Surgery Trust and the Department of Medicine, Wellington School of Medicine, New Zealand.
Plast Reconstr Surg. 2000 Sep;106(3):529-38. doi: 10.1097/00006534-200009030-00001.
Several cellular and extracellular markers that distinguish the phases of the hemangioma life cycle have been described previously. However, details of the phenotypic changes of; the various cellular elements during hemangioma development have not been fully reported, and the extracellular matrix composition, especially in the vicinity of the proliferating endothelial cells, is poorly described. This study examined the expression of cellular and extracellular molecules and cytokines in the proliferative, involuting, and involuted phases of hemangioma. Paraffin-embedded hemangioma specimens, four from each phase, were examined histochemically and immunohistochemically. Throughout the three phases, vascular endothelial cells stained positive for CD31 and von Willebrand factor, although in the involuted phase, not all vessels in the tissue expressed these endothelial markers. Proliferating cell nuclear antigen was expressed by the majority of endothelial cells and pericytes in the proliferative and early involuting phases, but its expression was negligible in the involuted phase. In addition to finding that the total number of mast cells was highest in the involuting phase, the authors observed that the proportion of chymase-positive mast cells decreased with the progression of hemangioma and that virtually all mast cells expressed the biogenic amine phenotype throughout the hemangioma life cycle. The localization of vascular endothelial growth factor predominantly to the pericytes and endothelial cells during the proliferative phase and of basic fibroblast growth factor to the endothelial cells in both the proliferative and early involuting phases is consistent with previous reports, although the latter growth factorwas also observed in mast cells. Type IV collagen and the beta chain of laminin and perlecan were detected in the basement membranes in all phases. Interestingly, collagen types I, III, and V were present in basal membranes throughout the phases and with increasing density in the stromal areas with involution, although type I collagen was less prominent during the proliferative phase. Short-chain collagen type VIII was localized extracellularly throughout the development of hemangioma but, during the early proliferative phase, it was also detected within mast cells. The expression of specific cytokines and cellular and extracellular markers may help distinguish the different clinical phases of the hemangioima life cycle. These results provide further insight into the biology of hemangioma.
先前已描述了几种区分血管瘤生命周期各阶段的细胞和细胞外标志物。然而，血管瘤发育过程中各种细胞成分的表型变化细节尚未得到充分报道，细胞外基质组成，尤其是增殖内皮细胞附近的组成，描述也很匮乏。本研究检测了血管瘤增殖期、消退期和消退后期细胞及细胞外分子和细胞因子的表达。对每个阶段各4个石蜡包埋的血管瘤标本进行了组织化学和免疫组织化学检查。在三个阶段中，血管内皮细胞CD31和血管性血友病因子染色均呈阳性，不过在消退期，组织中的并非所有血管都表达这些内皮标志物。增殖细胞核抗原在增殖期和早期消退期的大多数内皮细胞和周细胞中表达，但在消退后期其表达可忽略不计。除了发现肥大细胞总数在消退期最高外，作者还观察到，随着血管瘤进展，糜酶阳性肥大细胞的比例下降，并且在整个血管瘤生命周期中，几乎所有肥大细胞都表达生物胺表型。血管内皮生长因子在增殖期主要定位于周细胞和内皮细胞，碱性成纤维细胞生长因子在增殖期和早期消退期均定位于内皮细胞，这与先前报道一致，尽管在肥大细胞中也观察到了后一种生长因子。IV型胶原、层粘连蛋白β链和基底膜聚糖在所有阶段的基底膜中均有检测到。有趣的是，I、III和V型胶原在各阶段的基底膜中均有存在，且随着消退，基质区域的密度增加，不过I型胶原在增殖期不太明显。VIII型短链胶原在血管瘤整个发育过程中定位于细胞外，但在增殖早期，也在肥大细胞内检测到。特定细胞因子以及细胞和细胞外标志物的表达可能有助于区分血管瘤生命周期的不同临床阶段。这些结果为血管瘤生物学提供了进一步的见解。
