硝苯地平与苯妥英钠所致牙龈增生中p53蛋白和Ki-67抗原的表达

Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin.

作者信息

Saito K, Mori S, Tanda N, Sakamoto S

机构信息

Department of Preventive Dentistry, School of Dentistry, Tohoku University, Sendai, Japan.

出版信息

J Periodontol. 1999 Jun;70(6):581-6. doi: 10.1902/jop.1999.70.6.581.

DOI:10.1902/jop.1999.70.6.581

PMID:10397512

Abstract

BACKGROUND

Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied.

METHODS

We immunohistochemically examined the expression of tumor-related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method.

RESULTS

Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible.

CONCLUSIONS

The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression.

摘要

背景

尽管一直认为药物性牙龈增生与肿瘤发生无关，但最近的病例报告显示，环孢素和苯妥英钠所致的牙龈增生中可能会发生鳞状细胞癌。该疾病的发病机制与肿瘤发生之间的潜在关联尚未阐明，仍有待研究。

方法

我们采用抗生物素蛋白-生物素-过氧化物酶复合物法，对11例由硝苯地平及苯妥英钠所致的增生性牙龈组织以及5例对照组织进行免疫组化检测，观察肿瘤相关标志物如p53蛋白和Ki-67抗原的表达情况。

结果

在4例硝苯地平所致增生性牙龈组织标本中有2例，7例苯妥英钠所致增生性牙龈组织标本中有4例，其上皮细胞核中显示有p53蛋白表达，而5例非增生性对照组织的上皮中未观察到p53蛋白表达。p53蛋白免疫反应在增生上皮的基底层以上呈散在分布。增生性牙龈组织中表达Ki-67抗原的上皮细胞平均百分比比对照组织高10%以上。在增生性牙龈组织中深深延伸至固有层的典型钉突中，Ki-67抗原的表达受到抑制。在增生性牙龈组织的成纤维细胞中发现Ki-67抗原呈强免疫染色，而对照组织中则可忽略不计。