上皮细胞转分化与假性上皮瘤样肉芽肿

目的 探讨创伤愈合过程中上皮细胞转分化与假性上皮瘤样肉芽肿(PEG)发生之间的关系。方法将11例来自创(烧)伤后继发PEG病变(n=11)及其边缘正常皮肤(PEG-N,n=6)标本,采用组织病理学观察PEG上皮组织形态改变,并结合免疫组化和间接免疫荧光双标记技术,观察抗人广谱角蛋白(CKp)、CKl9、Ⅳ型胶原和层黏连蛋白(LM)、上皮细胞钙黏附蛋白(E-Cad)、B-连环蛋白(B．Cat)、黏着斑激酶(FAK)、干细胞因子(SCF)和受体(c-Kit)、增殖细胞核抗原(PCNA)、分化抗原簇-14(CD14)、CD68和肥大细胞类胰蛋白酶(MCT)在PEG组织中定位和分布特征。结果与PEG-N组相比,PEG呈现鳞状上皮化生,问质密布微血管结构和炎症细胞,可见上皮基底部结构崩溃、细胞顶,基极性丧失或减弱并有较多的细胞向间质迁移;超微结构显示上皮基底细胞变形、核／浆比增加和细胞问隙增宽,可见单核-巨噬细胞样细胞和肥大细胞样细胞原位“脱壳”样改变并与基底膜解离。在相同部位免疫标记显示基底细胞CKp、CKl9和E-Cad被显著下调,几乎不表达基底膜Ⅳ型胶原和LM成分,但对β-Cat和FAK有较高的免疫反应活性,并在上皮组织和问质内发现大小不一的CD14^ ．单核细胞、CD68^ 巨噬细胞、MCT^ -肥大细胞和CD68^ ／MCT^ -双阳性细胞,并有较强的SCF、c-Kit．和PCNA标记。结论在PEG形成过程中,普遍存在上皮细胞向单核一巨噬细胞和肥大细胞的转分化现象,可能与上皮较高的β-Cat／E-Cad信号落差和SCF-c-Kit信号通路被活化有关。上皮细胞向免疫细胞的异常取向可能是皮肤免疫系统过度动员的体现。上皮细胞跨胚层转分化机制将有助于肿瘤免疫和创伤修复失控机理的再认识。

Relationship between epithelial-immunologic cells transdifferentiation and pseudoepitheliomatous granuloma lesion

OBJECTIVE: Inappropriate treatment at early stage of wound could result in the formation of pseudoepitheliomatous granuloma (PEG). The correlation of abnormal transdifferentiation of epithelial cells to immunologic cells and the occurrence of PEG lesion was investigated. METHODS: Morphological change of epithelial tissue was observed with histopathology in 11 specimens of PEG lesions and 6 specimens of normal skins from PEG edge (PEG-N) from 11 patients with damaged skin. The expression characteristics and distribution of pan-cytokeratin (CKp), IV type collagen, laminin (LM), epithelial cadherin (E-Cad), beta-catenin (beta-Cat), focal adhesion kinase (FAK), stem cell factor (SCF) and its receptor-c-Kit, proliferating cell nuclear antigen(PCNA), and cluster of differentiation-14 (CD14), CD68 and mast cell tryptase (MCT) in PEG were detected with the immunohistochemical and the indirect immunofluorescent double-staining. RESULTS: In comparison with PEG-N, epithelial tissue take on squamous metaplasia, and stroma was infiltrated with intensive microvessels and inflammatory cells in the PEG lesion. Poor epithelial basal layer constitution, basal polarization, and migration of basal cells to stroma could be observed. In the ultrastructure, the loose intercellular junction of basal cells and the increased nucleus/cytoplasm ratio and intercellular space could be observed, neonatal monocytoid cells and macrophages and mast cells as a exuviate-like manner brooded from cytoplasm of original epithelial cells and basement membrane. protein expression of CKp and E-Cad by basal cells was significantly decreased, and the IV type collagen and LM protein could not be found in basement membrane of identical locus. By contrast, the immunoreactivity of beta-Cat and FAK was apparently increased. In addition, CD14(+) monocytes, CD68(+) macrophages, MCT(+) mast cells and CD68(+)/MCT(+) cells with various size, and these cells of stronger immuno-staining of SCF, c-Kit and PCNA antigen could be found in epithelial tissue and stroma. CONCLUSION: Epithelial cells in PEG related to wound are characteristized by transdifferentiation of epithelial cells to immunologic cells, wich may be associated with local infectious and inflammatory reaction, ultimately resulting in enhancement the ratio of beta-Cat/E-Cad signal and activation SCF-c-Kit signal pathway. The phenomena of transdifferentiation epithelial cells in the PEG lesion will help to recognize of the neoplatic immune and trauma repair mechanism.