POSSIBILITY OF CARCINOGENESIS IN DRUG-INDUCED GINGIVAL HYPERPLASIA

生长因子如转化生长因子β (TGF β)和碱性成纤维细胞生长因子（bFGF）已被证明与癌变过程有关。我们曾报道TGF β、bFGF及其受体可能与药物性牙龈增生的发病机制有关。本研究通过免疫组化方法检测了硝苯地平和苯妥英诱导的11例牙龈增生组织及5例对照组织上皮中p53蛋白、Ki-67抗原、表皮生长因子受体（EGF-R）等癌相关标志物的表达。硝苯地平诱导的4个标本和苯妥英诱导的7个标本中有4个标本上皮细胞核中表达p53蛋白，而5个非增生对照组织上皮中未见p53蛋白表达。对p53蛋白的免疫反应在增生性龈上皮的基底上层呈零星分布，与文献报道的邻近口腔癌的非肿瘤性上皮相似。增生性牙龈组织中表达Ki-67抗原的上皮细胞的平均百分比也比对照组高10%以上。结果与口腔发育不良上皮的研究结果相似。Ki-67抗原在增生性牙龈组织中表达受到抑制。另一方面，增生性牙龈组织中EGF-R的表达与对照组一样低。虽然牙龈增生通常被认为是一种非肿瘤性疾病，没有表现出上皮发育异常，但我们的研究结果表明，药物性牙龈增生可能与癌变的初始变化有关。

The growth factors such as transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) have been shown to be implicated in the processes of carcinogenesis. We have previously reported that TGF beta, bFGF and their receptors might be related to the pathogenesis of drug-induced gingival hyperplasia. In the present study, we examined immunohistochemically the expression of carcinoma-related markers such as p53 protein, Ki-67 antigen and epidermal growth factor erceptor (EGF-R) in the epithelia of 11 hyperplastic gingival tissues induced by nifedipine and phenytoin as well as 5 control tissues. Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic 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 layrs of hyperplastic gingival epithelium and was comparable to those in non-neoplastic epithelium adjacent to oral carcinoma indicated in the literatures.The mean percentage of epithelial cells experssing Ki-67 antigen in the hyperplastic gingival tissues was also more than 10% higher than that in the controls. The findings were comparable to those of oral dysplastic epithelia studies. The expression of Ki-67 antigen was suppressed in the rete pegs of hyperplastic gingival tissues. On the other hand, the expression of EGF-R in the hyperplastic gingival tissues was as low as the controls.Although gingival hyperplasia is generally thought to be a non-neoplastic disease and fails to show dysplastic epithelia, our results indicate the possibility that drug-induced gingival hyperplasia may be implcated in the initial changes of carcinogenesis.