Poulopoulos Athanasios K, Andreadis Dimitrios, Markopoulos Anastasios K
Athanasios K Poulopoulos, Dimitrios Andreadis, Anastasios K Markopoulos, Department of Oral Medicine and Oral Pathology, School of Dentistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
World J Exp Med. 2013 Aug 20;3(3):43-9. doi: 10.5493/wjem.v3.i3.43.
To investigate the role of matrix-degrading metalloproteinases 9, 12 (MMPs), as mediators of functional connective tissue damage in actinic cheilitis.
Thirty five formalin-fixed, paraffin embedded specimens of actinic cheilitis, and twelve specimens of normal lower lip vermillion, which were obtained by the archives of the Department of Oral Medicine and Maxillofacial Pathology, were examined. From each block, 5 μm thick sections were cut and routinely stained with Hematoxylin and Eosin. Immunohistochemical studies were performed on 4-μm thick sections of formalin-fixed paraffin embedded actinic cheilitis lesions and of normal lower lip vermillion, for MMP-9 and MMP-12 in serial sections of our specimens. Appropriate positive and negative controls were performed to confirm the specificity of the staining reaction. MMP immunohistochemistry was evaluated using a semiquantitative immunoreactive score.
Haematoxylin and eosin staining revealed in actinic cheilitis lesions atrophic stratified squamous cell epithelium, or focally and irregularly hyperplastic of variable thickness, in some areas was observed marked keratin production. Varying degrees of epithelial dysplasia were noticed with a wide spectrum of change within the same specimen. Characteristic was the appearance of chronic inflammatory infiltration, and a band of amorphous acellular, basophilic change like solar elastosis (elastin replacement of collagen). In normal lower lip specimens weak and scanty positive expression of MMP-9 and MMP-12 was observed. Anti-MMP-9 antibody showed a weak reaction, in actinic cheilitis lesions, focal in the elastotic material, in chronic inflammatory cells and mostly in macrophages and neutrophils. Strong and in some cases diffused immunohistochemical expression of MMP-12 was detected in actinic cheilitis lesions in the areas of the fragmented, distorted and thickened elastic fibers. MMP-12 was also expressed in chronic inflammatory cells and mostly macrophages. MMP-12 was significantly higher in actinic cheilitis specimens compared with the normal lower lip specimens (P = 0.0029).
Our results suggest that especially MMP-12 may play an important role in remodeling events occurring in the connective tissue during long-term exposure to sunlight in the actinic cheilitis lesions.
研究基质降解金属蛋白酶9、12(MMPs)作为光化性唇炎中功能性结缔组织损伤介质的作用。
检查了从口腔医学与颌面病理学系档案中获取的35例光化性唇炎的福尔马林固定、石蜡包埋标本,以及12例正常下唇唇红标本。从每个组织块切取5μm厚的切片,常规苏木精和伊红染色。对福尔马林固定石蜡包埋的光化性唇炎病变和正常下唇唇红的4μm厚切片进行免疫组织化学研究,检测连续切片中的MMP-9和MMP-12。进行适当的阳性和阴性对照以确认染色反应的特异性。使用半定量免疫反应评分评估MMP免疫组织化学。
苏木精和伊红染色显示,光化性唇炎病变中有萎缩性复层鳞状上皮,或局部和不规则增厚的增生,在某些区域观察到明显的角质形成。在同一标本中发现不同程度的上皮发育异常,变化范围广泛。其特征是出现慢性炎症浸润,以及一条无定形、无细胞、嗜碱性改变的带,类似日光性弹力纤维变性(弹性蛋白替代胶原蛋白)。在正常下唇标本中观察到MMP-9和MMP-12的弱阳性和少量阳性表达。抗MMP-9抗体在光化性唇炎病变中显示弱阳性反应,在弹力纤维变性物质中呈局灶性,在慢性炎症细胞中,主要在巨噬细胞和中性粒细胞中。在光化性唇炎病变中,在弹性纤维破碎、扭曲和增厚的区域检测到MMP-12的强免疫组织化学表达,在某些情况下呈弥漫性表达。MMP-12也在慢性炎症细胞中表达,主要是巨噬细胞。与正常下唇标本相比,光化性唇炎标本中的MMP-12显著更高(P = 0.0029)。
我们的结果表明,特别是MMP-12可能在光化性唇炎病变长期暴露于阳光下期间结缔组织中发生的重塑事件中起重要作用。