Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization
Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization
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DOI：
10.1038/modpathol.3800753
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发表时间：
2007-03-01
期刊：
影响因子：
7.5
通讯作者：
Tomita, Yasuhiko
中科院分区：
文献类型：
--
作者：
Toyosawa, Satoru;Yuki, Michiko;Tomita, Yasuhiko
颌骨骨化性纤维瘤和颌骨纤维结构不良是颌面部纤维骨性病变，应由病理学家加以鉴别，因为它们表现出不同的疾病发展模式。然而，这两种病变往往表现出相似的组织学和放射学特征，这使得两者之间的区别成为诊断的两难境地。在本研究中，我们对具有典型组织学和放射学特征的5例骨化性纤维瘤、4例颌外纤维异常增殖症和5例颌骨纤维异常增殖症进行了免疫学和分子分析。首先，我们研究了纤维异常增生症和骨化性纤维瘤在Runx2(决定间充质干细胞成骨分化)和其他成骨标志物表达上的差异。纤维异常增生症和骨化性纤维瘤中的成纤维细胞在细胞核内有较强的Runx2表达。除骨钙素外，两种病变的骨基质对所有检测标记物的表达模式相似。骨钙素在纤维异常增生症的钙化区呈强阳性反应，而在骨化性纤维瘤病变中呈弱阳性反应。其次，我们对刺激G蛋白基因(GNAS)的α亚基的Arg(201)密码子的突变进行了肽核酸(PNA)的聚合酶链式反应(PCR)分析，该基因被报道为颌外纤维异常增殖症的标志。9例颌外或颌骨纤维异常增生症均为该突变阳性。另一方面，五例骨化性纤维瘤中没有一例显示出突变。这些发现表明，尽管纤维异常增生症和骨化性纤维瘤是相似的疾病实体，尤其是在基质成纤维细胞样细胞中显示成骨谱系，但它们表现出明显的差异，这可以通过免疫组织化学检测骨钙素的表达来揭示。此外，用聚合酶链式反应分析精氨酸(201)密码子上的GNAS突变是鉴别纤维异常增生症和骨化性纤维瘤的有用方法。
Ossifying fibroma and fibrous dysplasia of the jaw are maxillofacial fibro-osseous lesions that should be distinguished each other by a pathologist because they show distinct patterns of disease progression. However, both lesions often show similar histological and radiological features, making distinction between the two a diagnostic dilemma. In this study, we performed immunological and molecular analyses of five ossifying fibromas, four cases of extragnathic fibrous dysplasia, and five cases of gnathic fibrous dysplasia with typical histological and radiographic features. First, we examined the difference between fibrous dysplasia and ossifying fibroma in the expression of Runx2 (which determined osteogenic differentiation from mesenchymal stem cells) and other osteogenic markers. Fibroblastic cells in fibrous dysplasia and ossifying fibroma showed strong Runx2 expression in the nucleus. The bone matrices of both lesions showed similar expression patterns for all markers tested except for osteocalcin. Immunoreactivity for osteocalcin was strong throughout calcified regions in fibrous dysplasia, but weak in ossifying fibroma lesions. Second, we performed PCR analysis with peptide nucleic acid (PNA) for mutations at the Arg(201) codon of the alpha subunit of the stimulatory G protein gene (GNAS), which has reported to be a marker for extragnathic fibrous dysplasia. All nine cases of extragnathic or gnathic fibrous dysplasia were positive for this mutation. On the other hand, none of the five cases of ossifying fibroma showed the mutation. These findings indicate that although fibrous dysplasia and ossifying fibroma are similar disease entities, especially in the demonstration of the osteogenic lineage in stromal fibroblast-like cells, they show distinct differences that can be revealed by immunohistochemical detection of osteocalcin expression. Furthermore, PCR analysis with PNA for GNAS mutations at the Arg(201) codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma.