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口腔黏膜下纤维化中上皮生长分数及p53肿瘤抑制基因的表达

Epithelial growth fraction and expression of p53 tumour suppressor gene in oral submucous fibrosis.

作者信息

Cox S C, Walker D M

机构信息

Faculty of Dentistry, University of Sydney, Westmead Hospital Dental Clinical School.

出版信息

Aust Dent J. 1996 Apr;41(2):91-6. doi: 10.1111/j.1834-7819.1996.tb05920.x.

DOI:10.1111/j.1834-7819.1996.tb05920.x
PMID:8670041
Abstract

The incidence of squamous cell carcinoma in patients with oral submucous fibrosis (OSF) exceeds 7 per cent. The proliferative cell nuclear antigen (PCNA) is a convenient marker of epithelial cell proliferation and p53 tumour suppressor gene mutations or deletions are frequent in oral cancer. The present study estimated the basal epithelial cell growth fraction using a standard immunohistological method for the detection of nuclear PCNA from 20 Nepalese patients with OSF as 31.8 per cent compared with 7.6 per cent for oral mucosa from 43 normal subjects (p < 0.001) and 39.4 per cent for 44 patients with oral cancer. The PCNA growth fraction correlated significantly with that derived by Ki-67 labelling. There was no correlation between the growth fraction and the severity of epithelial dysplasia found is OSF. Abnormal expression of p53 protein identified by immunohistochemistry with a panel of antibodies was found in 70 per cent of the OSF specimens, and 21 per cent of mucosal specimens from subjects with clinically normal mouths. PCNA-positive cells and p53 expression were restricted to the basal epithelial layer in OSF. The unexpected finding of p53 protein in clinically healthy mucosa was confined to subjects aged over 40 years who smoked tobacco, a known risk factor for oral cancer. There was no association between p53 expression and epithelial atypia scores in OSF. It is concluded that the proportion of actively cycling epithelial cells is increased in OSF and that p53 tumour suppressor gene mutations or deletions may be prevalent. Confirmation by molecular biology techniques of this genetic damage is now needed.

摘要

口腔黏膜下纤维化(OSF)患者中鳞状细胞癌的发病率超过7%。增殖细胞核抗原(PCNA)是上皮细胞增殖的便捷标志物,p53肿瘤抑制基因突变或缺失在口腔癌中很常见。本研究采用标准免疫组织学方法检测核PCNA,估计了20例尼泊尔OSF患者的基底上皮细胞生长分数为31.8%,而43名正常受试者的口腔黏膜为7.6%(p<0.001),44例口腔癌患者为39.4%。PCNA生长分数与Ki-67标记得出的结果显著相关。生长分数与OSF中发现的上皮发育异常严重程度之间没有相关性。用一组抗体通过免疫组织化学鉴定的p53蛋白异常表达在70%的OSF标本以及21%临床口腔正常受试者的黏膜标本中被发现。OSF中PCNA阳性细胞和p53表达局限于基底上皮层。在临床健康黏膜中意外发现的p53蛋白仅限于40岁以上吸烟的受试者,吸烟是口腔癌的已知危险因素。OSF中p53表达与上皮异型性评分之间没有关联。结论是OSF中活跃循环的上皮细胞比例增加,p53肿瘤抑制基因突变或缺失可能普遍存在。现在需要通过分子生物学技术对这种基因损伤进行确认。

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