Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ : an aid for histopathologic recognition of their cell proliferation centers
Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ : an aid for histopathologic recognition of their cell proliferation centers
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基质金属蛋白酶7和基底膜蛋白聚糖在口腔上皮发育不良和原位癌中的作用：有助于组织病理学识别其细胞增殖中心
DOI：
10.1111/j.1600-0714.2009.00750.x
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发表时间：
2009
影响因子：
3.3
通讯作者：
Saku T.
中科院分区：
文献类型：
--
作者：
Tilakaratne WM;Kobayashi T;Ida-Yonemochi H;Swelam W;Yamazaki M;Mikami T;Alvarado CG;Ahsan MS;Maruyama S;Cheng J;Saku T.
背景：作为鉴别口腔上皮异型增生、原位癌和鳞癌的有价值的工具之一，我们提出了硫酸乙酰肝素蛋白多糖(HSPG)的免疫组织化学方法。由于HSPGs是基质金属蛋白酶(MMP7)的细胞外对接分子，我们的目的是确定MMP7在这些病变中的表达模式，以期为口腔交界性恶性肿瘤的诊断提供可能的帮助。方法：采用免疫组织化学方法检测20例中度异型增生、CIS、SCC和正常/增生/轻度异常舌黏膜和颊粘膜中MMP1、MMP2和MMP7的表达。最显著的发现是基质金属蛋白酶-7在上皮性异型增生中强表达，呈双期表现：明晰地将基质金属蛋白酶-7免疫阳性(+)的下层异型/碱样细胞与非阳性的上层角化细胞区分开来。MMP-7+细胞分布于CIS的整个上皮层。在鳞状细胞癌中，癌细胞中的MMP7阳性表达减弱，而间质细胞中出现MMP7的表达。这些基质金属蛋白酶-7的表达谱与Perlecan相似。结论：在口腔黏膜上皮细胞恶变过程中，与基质金属蛋白酶相关的Perlecan代谢增强在细胞增殖过程中起重要作用，免疫组织化学方法检测口腔粘膜上皮细胞增殖中心可能有助于确定口腔扁平苔藓和异型增生的细胞增殖中心。
Background:As one of the valuable tools for differential diagnoses of oral epithelial dysplasia, carcinomain situ(CIS) and squamous cell carcinoma (SCC), we have proposed the immunohistochemistry for perlecan, a heparan sulfate proteoglycan (HSPG). As HSPGs have been shown to be extracellular docking molecules for matrix metalloproteinase (MMP) 7, our aim was to determine the expression mode of MMP‐7 in these lesions for its possible diagnostic aid for oral borderline malignancies.Methods:Twenty cases each of moderate dysplasia, CIS, SCC, and normal/hyperplastic/mild dysplastic epithelia of the tongue and buccal mucosa were immunohistochemically examined for MMP‐1, ‐2 and ‐7 in reference to their perlecan immunolocalization.Results:The expression of all three MMPs in the normal mucosal epithelium was restricted mainly to the parabasal layers. The most striking finding was strong expression of MMP‐7 in epithelial dysplasia with a two‐phase appearance: a clear demarcation of MMP‐7‐immunopositive (+) lower dysplastic/basaloid cells from non‐positive upper keratinized cells. MMP‐7+ cells were spread over the whole epithelial layer of CIS. In SCC, MMP‐7 positivity was reduced from carcinoma cells but instead appeared in stromal cells. These expression profiles of MMP‐7 resembled those of perlecan. MMP‐1 and MMP‐2 exhibited a similar but much weaker staining than MMP‐7.Conclusion:These results suggest that the enhanced metabolism of perlecan associated with MMP‐7 plays an important role in the cell proliferation of oral epithelia in their malignant transformation process, and that MMP‐7 immunohistochemistry may be a valuable aid for identification of the cell proliferation center in oral CIS and dysplasia.