Kushner J, Bradley G, Jordan R C
Department of Oral Pathology, Faculty of Dentistry, University of Toronto, Canada.
J Pathol. 1997 Dec;183(4):418-23. doi: 10.1002/(SICI)1096-9896(199712)183:4<418::AID-PATH946>3.0.CO;2-T.
Oral squamous cell carcinoma develops through a series of precancerous stages manifested at the microscopic level as epithelial dysplasia. Mutation of the p53 tumour suppressor gene is thought to be an important component of oral carcinogenesis. p53 regulates cell proliferation and DNA repair by inhibiting the cell cycle at G1/S; loss of p53 function may therefore lead to aberrant cell kinetics. To date, no studies have examined the relationship between p53 protein and alterations in cell kinetics in oral epithelial dysplasia from a single anatomical site. Serial sections were studied from 40 routinely processed biopsy specimens of epithelial dysplasia from the floor of the mouth. The expression of p53 protein was determined by immunohistochemistry and cell proliferation was studied by immunostaining for the cell cycle-dependent protein Ki-67. The number of positive cells per millimetre of basement membrane was determined using computer image analysis and compared with site-matched normal controls. The mean p53 labelling index (LI) in normal mucosa was low, 3.48 +/- 0.92 [mean +/- 95 per cent confidence interval (CI)], and increased sharply in the transition from mild (42.49 +/- 21.71) to moderate (104.86 +/- 51.39) epithelial dysplasia. The mean p53 LI for severe dysplasia was 119.09 +/- 56.50. Differences were also observed in the distribution of p53-positive cells between grades of dysplasia, with the development of compact p53-positive foci in severe dysplasia. Mean proliferative indices, as determined by Ki-67 expression, were significantly associated with grade of epithelial dysplasia. Furthermore, there was a significant correlation between p53 LI and Ki-67 score (r2 = 0.37, P = 0.01). It is concluded that altered p53 protein expression is probably an early event in oral carcinogenesis in the floor of the mouth and is associated with dysregulation of cell proliferation at this site.
口腔鳞状细胞癌通过一系列癌前阶段发展而来，在微观层面表现为上皮发育异常。p53肿瘤抑制基因的突变被认为是口腔癌发生的一个重要组成部分。p53通过在G1/S期抑制细胞周期来调节细胞增殖和DNA修复；因此，p53功能丧失可能导致异常的细胞动力学。迄今为止，尚无研究从单一解剖部位探讨口腔上皮发育异常中p53蛋白与细胞动力学改变之间的关系。对40例来自口底的常规处理的上皮发育异常活检标本的连续切片进行了研究。通过免疫组织化学测定p53蛋白的表达，并通过对细胞周期依赖性蛋白Ki-67进行免疫染色来研究细胞增殖。使用计算机图像分析确定每毫米基底膜的阳性细胞数量，并与部位匹配的正常对照进行比较。正常黏膜中的平均p53标记指数（LI）较低，为3.48±0.92[平均值±95%置信区间（CI）]，在从轻度（42.49±21.71）到中度（104.86±51.39）上皮发育异常的转变过程中急剧增加。重度发育异常的平均p53 LI为119.09±56.50。在发育异常的不同等级之间，p53阳性细胞的分布也观察到差异，在重度发育异常中出现紧密的p53阳性灶。由Ki-67表达确定的平均增殖指数与上皮发育异常的等级显著相关。此外，p53 LI与Ki-67评分之间存在显著相关性（r2 = 0.37，P = 0.01）。结论是，p53蛋白表达改变可能是口底口腔癌发生的早期事件，并与该部位细胞增殖失调有关。
