Ohashi Amiko, Ishizaki Masamichi, Kawana Seiji, Fukuda Yuh
Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
Pathol Int. 2004 Aug;54(8):585-94. doi: 10.1111/j.1440-1827.2004.01667.x.
Transepithelial elimination of elastic fibers is frequently seen in keratoacanthoma. However, the mechanism underlying this elastic fiber transport is not yet fully understood. We investigated the process by comparing the related features of 27 cases of keratoacanthoma, eight cases of squamous cell carcinoma and 11 cases of seborrheic keratosis (control). Microscopically, transepithelial elimination of elastic fibers was specifically observed in keratoacanthomas. Elastic fibers were surrounded by keratoacanthoma cell membrane and were ultrastructurally associated with hemidesmosomes and the basement membrane. Collagen fibrils were also observed within small, membrane-delineated vesicles within cells in the lower layers of the tumor. Also noted was strong expression of matrix metalloproteinase-1, which was detected by immunohistochemical analysis and in situ hybridization. Western blotting showed significantly stronger labeling of matrix metalloproteinase-1 in samples of keratoacanthoma than in normal epidermis. In contrast, squamous cell carcinomas and seborrheic keratosis exhibited none of the aforementioned characteristics. We propose that keratoacanthoma cells entrap, lift and eliminate elastic fibers as they proliferate and keratinize toward the epidermal surface, while simultaneously phagocytosing collagen fibrils. In that regard, matrix metalloproteinase-1 appears to play a key role in the degradation of collagen fibrils.
弹力纤维经上皮消除现象在角化棘皮瘤中屡见不鲜。然而，这种弹力纤维转运的潜在机制尚未完全明确。我们通过比较27例角化棘皮瘤、8例鳞状细胞癌及11例脂溢性角化病（对照）的相关特征来研究这一过程。显微镜下，仅在角化棘皮瘤中特异性观察到弹力纤维的经上皮消除现象。弹力纤维被角化棘皮瘤细胞膜包绕，超微结构上与半桥粒及基底膜相关。在肿瘤下层细胞内的小的、膜界定的囊泡中也观察到了胶原纤维。免疫组化分析和原位杂交检测还发现基质金属蛋白酶-1表达强烈。蛋白质印迹法显示角化棘皮瘤样本中基质金属蛋白酶-1的标记明显强于正常表皮。相比之下，鳞状细胞癌和脂溢性角化病均未表现出上述特征。我们提出，角化棘皮瘤细胞在向表皮表面增殖和角质化的过程中捕获、提升并消除弹力纤维，同时吞噬胶原纤维。在这方面，基质金属蛋白酶-1似乎在胶原纤维的降解中起关键作用。
