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Analyzes of p16/CDKN2.p53 and ras gene mutations with cell-proliferative activities in oral squamous cell carcinomas and the premalignant lesions

口腔鳞癌及癌前病变中p16/CDKN2.p53和ras基因突变与细胞增殖活性的分析

基本信息

批准号：
06672011
负责人：
SUGIMURA Masahito
金额：
$ 1.22万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672011/
关键词：
oral tumor premalignant cell proliferation p16 CDKN2 p53 ras cell proliferation oral PCNA AgNoR SSCP premalignant lesions S.C.C.

项目摘要

p16/CDKN2, p53 and ras gene mutations were examined using a combination of immunohistochemistry and SSCP-Sequence analyzes with cell proliferative activities such as PCNA and AgNOR in 20 oral squamous cell carcinomas and 20 oral premalignant lesions. The p16/CDKN2 gene mutations were found 2 of 20 cases squamous cell carcinoma, but none of premalignant lesions. Two cases with p16/CDKN2 gene deletions were detected with immunonegative staining for p16 protein. The p53 gene mutations were found 5 of 20 squamous cell carcinoma and none of premalignant lesions. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples.On the other hand, 35% (7/20) of the oral squamous cell carcinomas demonstrated immunoreactivity for p53 and 50% were immunopositive for ras p21. Two cases with positive staining for p53 in moderate dysplasia and hyperplasia, without p53 gene mutation, were relatively light and seemed to be limited to a few cells within the basal cell layr. PCNA and AgNOR values revealed high scores in these cases, it is suggested that p53 expression may be related to accumulation of wild type protein with rapid cell proliferation rather than gene mutation. The PCNA and AgNOR score tend to be significantly higher in the carcinomas than those in premalignant lesions. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences and that genetic alterations of the ras genes may not play a significant role in human oral tumorigenesis. The tumor suppressor gene such as p16/CDKN2 or p53 seem to be not only independently occurred but involved in later events of oral tumorigenesis.

应用免疫组化结合SSCP-序列分析技术，检测20例口腔鳞癌及20例癌前病变中p16/CDKN 2、p53和ras基因突变，并结合细胞增殖活性（PCNA、AgNOR）进行分析。20例鳞状细胞癌中有2例p16/CDKN 2基因突变，而癌前病变中无一例p16/CDKN 2基因突变。p16蛋白免疫阴性染色检测到2例p16/CDKN 2基因缺失。20例鳞癌中有5例p53基因突变，未发现癌前病变。K-ras基因突变在单个癌和不典型增生中被发现，另一方面，35%（7/20）的口腔鳞状细胞癌显示p53和50%的rasp 21免疫阳性。2例中度不典型增生和增生的p53阳性染色，无p53基因突变，染色较浅，似乎局限于基底细胞层内的少数细胞。PCNA和AgNOR值显示这些病例中的高评分，提示p53表达可能与细胞快速增殖的野生型蛋白积聚有关，而不是基因突变。PCNA和AgNOR评分在癌组织中明显高于癌前病变。从数据中，可以认为，p16/CDKN 2和p53突变是相对较晚发生的，ras基因的遗传改变可能不会在人类口腔肿瘤发生中发挥重要作用。抑癌基因如p16/CDKN 2或p53似乎不仅独立发生，而且参与了口腔肿瘤发生的后期事件。