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口腔扁平苔藓中的细胞周期调控机制:上皮细胞发生恶性转化的分子基础。

Cell cycle regulating mechanisms in oral lichen planus: molecular bases in epithelium predisposed to malignant transformation.

作者信息

González-Moles M A, Bascones-Ilundain C, Gil Montoya J A, Ruiz-Avila I, Delgado-Rodríguez M, Bascones-Martínez A

机构信息

School of Dentistry, Granada University, Paseo de Cartuja s/n, 18071 Granada, Spain.

出版信息

Arch Oral Biol. 2006 Dec;51(12):1093-103. doi: 10.1016/j.archoralbio.2006.06.007. Epub 2006 Aug 17.

Abstract

OBJECTIVE

Expression of p53, p21, ki-67, Bcl-2 and caspase-3 proteins in oral lichen planus (OLP) was studied to investigate cell cycle regulation mechanisms in this disease.

MATERIAL AND METHODS

Oral biopsies were obtained from 51 patients with OLP and 26 controls for immunohistochemical analysis (peroxidase antiperoxidase) to quantify expression of the proteins under study (-: 0%, +: <10%, ++: 10-25%, +++: 26-50%, ++++: >50% positive cells).

RESULTS

Basal expression of caspase-3 was negative in 22 cases (46.8%) and positive in <10% of basal cells in 22 cases (46.8%); caspase-3 expression in inflammatory infiltrate was negative in 22 cases (46.8%) and positive in <10% of lymphocytes in 20 cases (42.5%). Basal expression of Bcl-2 was negative in 35 cases (74.5%); Bcl-2 was expressed in inflammatory infiltrate in 34 cases (72.3%) and was positive in <25% of lymphocytes in 14 of these (29.7%). Basal expression of p53 and p21 was positive in 32 (67.9%) and 23 (48.8%) cases, respectively. Basal expression of ki-67 was positive in 45 cases (95.7%), of which 20 (42.5%) showed positivity in >25% of cells; ki-67 was expressed in inflammatory infiltrate in 23 cases (48.9%). Significant associations were found between basal expressions of p53 and ki-67 (p<0.001) and between Bcl-2 expression in infiltrate and basal expression of ki-67 (p<0.001). No association was observed between basal expressions of p53 and caspase-3 (p=0.08). Bcl-2 expression in infiltrate and basal expression of ki-67 were independently associated with presence of OLP.

CONCLUSIONS

Epithelial cells in OLP do not preferentially develop apoptosis but rather cycle arrest or an increased proliferation rate, which may create a suitable substrate for malignant transformation.

摘要

目的

研究p53、p21、ki-67、Bcl-2和caspase-3蛋白在口腔扁平苔藓(OLP)中的表达,以探讨该疾病的细胞周期调控机制。

材料与方法

从51例OLP患者和26例对照者获取口腔活检组织进行免疫组织化学分析(过氧化物酶抗过氧化物酶法),以量化所研究蛋白的表达情况(-:0%,+:<10%,++:10 - 25%,+++:26 - 50%,++++:>50%阳性细胞)。

结果

caspase-3的基底表达在22例(46.8%)中为阴性,在22例(46.8%)的基底细胞中<10%为阳性;炎症浸润中caspase-3的表达在22例(46.8%)中为阴性,在20例(42.5%)的淋巴细胞中<10%为阳性。Bcl-2的基底表达在35例(74.5%)中为阴性;34例(72.3%)的炎症浸润中有Bcl-2表达,其中14例(29.7%)的淋巴细胞中<25%为阳性。p53和p21的基底表达分别在32例(67.9%)和23例(48.8%)中为阳性。ki-67的基底表达在45例(95.7%)中为阳性,其中20例(42.5%)的细胞中>25%为阳性;23例(48.9%)的炎症浸润中有ki-67表达。p53和ki-67的基底表达之间(p<0.001)以及浸润中Bcl-2表达和ki-67的基底表达之间(p<0.001)存在显著相关性。p53和caspase-3的基底表达之间未观察到相关性(p = 0.08)。浸润中Bcl-2表达和ki-67的基底表达与OLP的存在独立相关。

结论

OLP中的上皮细胞并非优先发生凋亡,而是出现细胞周期停滞或增殖率增加,这可能为恶性转化创造合适的底物。

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