Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation

Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation
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DOI:
10.1111/j.1600-0714.2005.00376.x
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发表时间:
2006-01-01
影响因子:
3.3
通讯作者:
Nylander, K
Nylander, K
中科院分区:
医学3区
文献类型:
--
作者:
Ebrahimi, M;Wahlin, YB;Nylander, K

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背景:口腔扁平苔藓(OLP)和移植物vs.-宿主疾病(GVHD)是具有向头颈部鳞状细胞癌(SCCHN)的恶性转化的增加的风险的病症。p63基因编码6种不同的蛋白质,在SCCHN中高水平表达。方法:使用区分正常上皮中表达的主要亚型的抗体,分析诊断为OLP和GVHD患者的活检组织中的p63蛋白表达,同时分析正常颊粘膜和SCCHN的活检组织。与正常粘膜相比,在OLP和GVHD中,所有p63亚型的表达均降低,而p53蛋白的表达上调。在SCCHN中,p63大量表达,一些肿瘤显示出强烈的p53染色,提示p53 mutation.CONCLUSIONS:p63的减少和p53的表达增加,OLP和GVHD表明这两个相关蛋白的协调作用,以保护口腔粘膜免受潜在炎症的破坏性影响。在SCCHN中,已经观察到TP 53基因的破坏和某些p63亚型的过度表达,表明这可能导致肿瘤转化。
BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN.METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN.RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation.CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.