RANK, RANKL, and OPG in recurrent solid/multicystic ameloblastoma: their distribution patterns and biologic significance

RANK, RANKL, and OPG in recurrent solid/multicystic ameloblastoma: their distribution patterns and biologic significance
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DOI:
10.1016/j.oooo.2014.09.017
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发表时间:
2015-01-01
影响因子:
2.9
通讯作者:
Ng, Kok Han
Ng, Kok Han
中科院分区:
医学4区
文献类型:
--
作者:
Siar, Chong Huat;Tsujigiwa, Hidetsugu;Ng, Kok Han

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目标.确定骨吸收调节因子、核因子κ B受体激活因子(RANK)、RANK配体(RANKL)和骨保护素(OPG)在复发性成釉细胞瘤(RA)中的分布模式,并阐明其对这些肿瘤生物学行为的影响。对15例RA石蜡包埋标本进行RANK、RANKL和OPG的免疫组化检测。在RA样本中检测到不均匀的RANK-RANKL-OPG三联体。破骨细胞分化所必需的RANK在肿瘤上皮中强烈表达。相反,RANKL,破骨细胞激活剂,明显表达不足,蛋白定位主要是间质。OPG是一种破骨细胞生成抑制因子,在肿瘤上皮中比在基质中检测到更多,表明RANKL的功能失活。大多数RA(n = 12/15; 80%)表现出双分子空间表达模式,最常见的是RANK阳性/OPG阳性(n = 8/15; 53.3%)。三种蛋白与RA患者的临床/病理参数均无显著相关性(P > 0.05)。在RA中观察到的RANK(+)/RANKL(低/-)/OPG(+)表型表明这些复发性肿瘤中局部骨代谢改变,其特征为骨吸收活性降低。
Objectives. To determine the distribution patterns of bone resorption regulators, receptor activator of nuclear factor kappa-B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in recurrent ameloblastoma (RAs) and to clarify their impact on the biologic behavior of these neoplasms.Materials and Methods. Fifteen paraffin-embedded RA cases were subjected to immunohistochemistry for expression of RANK, RANKL, and OPG.Results. The RANK-RANKL-OPG triad was heterogeneously detected in RA samples. RANK, essential for osteoclast differentiation, was strongly expressed in tumoral epithelium. Conversely, RANKL, an osteoclast activator, was markedly underexpressed, and protein localization was predominantly stromal. OPG, an osteoclastogenesis inhibitory factor, was detected in neoplastic epithelium more than in stroma, suggesting functional inactivation of RANKL. Most RA (n = 12/15; 80%) exhibited a bimolecular spatial expression pattern, the most common being RANK-positive/OPG-positive (n = 8/15; 53.3%). All three proteins showed no significant correlation with the clinical/histopathologic parameters in RA patients (P > .05).Conclusions. The RANK(+)/RANKL(low/-)/OPG(+) phenotype observed in RA suggests an altered local bonemetabolism characterized by low bone resorptive activity in these recurrent tumors.