Ikarashi Terué, Ida-Yonemochi Hiroko, Ohshiro Kazufumi, Cheng Jun, Saku Takashi
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Oral Pathol Med. 2004 Feb;33(2):87-95. doi: 10.1111/j.1600-0714.2004.00026.x.
Intercellular deposition of perlecan, a major heparan sulfate proteoglycan (HSPG) of the basement membrane, is known to result in characteristic stellate reticulum-like structures in ameloblastomas or tooth germs. Although enlargement of the intercellular space is one of the histological characteristics of epithelial dysplasia of oral mucosa, the mode of expression of perlecan is poorly understood in these epithelial lesions.
Eighty-two biopsy specimens consisting of normal and hyperplastic epithelium, epithelial dysplasia, and squamous cell carcinomas were examined for both perlecan core protein and heparan sulfate (HS) chains by immunohistochemistry and in situ hybridization.
In normal and hyperplastic epithelium, perlecan core protein and HS chains were localized in the cell border of parabasal cells and lower prickle cells, and HS chains were also found in basal cells. With an increase in the severity of epithelial dysplasia, the core protein was heavily and extensively deposited in the interepithelial space as well as in the cytoplasm of epithelial cells from the basal to the surface layers. Its gene expression was confirmed in the cells around the protein deposits. On the other hand, HS chains were enhanced in mild dysplasia, but decreased in moderate and severe dysplasias. In squamous cell carcinomas, either the core protein or HS chains were found scarcely in tumor cells but abundantly in the stromal space.
The findings indicate that perlecan is localized in the intercellular space of the oral epithelia, and that it is over-expressed in dysplastic epithelial cells and is deposited in their interepithelial space, which results in the histology of reduction of cellular cohesion.
基底膜的主要硫酸乙酰肝素蛋白聚糖（HSPG）——基底膜聚糖的细胞间沉积，已知会在成釉细胞瘤或牙胚中形成特征性的星网状结构。尽管细胞间隙增大是口腔黏膜上皮发育异常的组织学特征之一，但在这些上皮病变中，基底膜聚糖的表达模式仍知之甚少。
通过免疫组织化学和原位杂交，对82份由正常和增生上皮、上皮发育异常及鳞状细胞癌组成的活检标本进行基底膜聚糖核心蛋白和硫酸乙酰肝素（HS）链检测。
在正常和增生上皮中，基底膜聚糖核心蛋白和HS链定位于基底旁细胞和较低棘层细胞的细胞边界，在基底细胞中也发现有HS链。随着上皮发育异常严重程度的增加，核心蛋白大量广泛沉积于上皮间间隙以及从基底层到表层的上皮细胞胞质中。在蛋白沉积物周围的细胞中证实有其基因表达。另一方面，HS链在轻度发育异常中增强，但在中度和重度发育异常中减少。在鳞状细胞癌中，肿瘤细胞中几乎未发现核心蛋白或HS链，但在间质中大量存在。
这些发现表明，基底膜聚糖定位于口腔上皮的细胞间间隙，在发育异常的上皮细胞中过度表达并沉积于上皮间间隙，导致细胞黏附性降低的组织学表现。
