Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia.

Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia.
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DOI:
10.1016/s1368-8375(01)00119-1
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发表时间:
2002-09
期刊:
影响因子:
4.8
通讯作者:
Yuichiro Okazaki;Youichi Tanaka;M. Tonogi;G. Yamane
Yuichiro Okazaki;Youichi Tanaka;M. Tonogi;G. Yamane
中科院分区:
医学2区
文献类型:
--
作者:
Yuichiro Okazaki;Youichi Tanaka;M. Tonogi;G. Yamane

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用4-硝基喹啉-1-氧化物(4NQO)诱发大鼠早期舌癌模型,探讨异型增生恶变的早期诊断。将大鼠舌病变按严重程度分为早期癌组、异型增生组和无变化组。根据WHO上皮异型增生标准中的13项判定上皮病变程度。用免疫组织化学方法检测P53和Bcl2蛋白的表达水平,用TUNEL法检测细胞的凋亡率。此外,还检测到由病变引起的P53突变。P53蛋白在不典型增生中高表达,在早期癌和不典型增生中高表达。TUNEL阳性细胞主要见于无变化细胞的颗粒层,随着细胞向癌早期转移,阳性细胞数量逐渐减少。用显微解剖方法在异型增生中检测到P53突变,9个病变中有3个发现了P53突变。在异型增生中检测到的所有突变都位于在早期癌症中发现突变的同一密码子上。这些结果表明,P53基因突变与癌前病变的组织学改变之间有很强的相关性,P53和Bcl2阳性上皮的鉴定和TUNEL阳性率的降低都有助于癌前病变的恶性潜能的诊断。
A study was conducted in rats with early tongue carcinoma induced by 4-nitroquinoline 1-oxide (4NQO), in order to investigate the early diagnosis of malignant potential of epithelial dysplasia. The rat tongue lesions were classified by their severity into three groups corresponding to early cancer, dysplasia and no change. The grade of epithelial changes was determined according to 13 items of WHO Epithelial Dysplasia Criteria. The expression levels of p53 and Bcl-2 proteins were detected immunohistochemically, and apoptotic cells were detected using the TUNEL method. In addition, a p53 mutation by lesions was detected. The expression ratio of p53 protein was high in dysplasia, and the ratio of Bcl-2 protein was high in early cancer and dysplasia. The TUNEL-positive cells were observed primarily in the granular layers of the no change cells, and their numbers decreased as the cells shifted to the early cancer stage. The p53 mutation was detected using a microdissection method in dysplasia, where it was found in three out of nine lesions. All the mutations in dysplasia detected were on the same codon that was found to be mutated in the early cancer. These results indicate that the association between the p53 mutation and histological changes in carcinogenesis epithelial dysplasia is strong, and that both the identification of p53- and Bcl-2-positive epithelium, and decrease in the TUNEL positive ratio, were useful for the diagnosis of the malignant potential of precancerous lesions.