Molecular pathological analysis of oral carcinoma caused by chewing habits in Asia

亚洲咀嚼习惯所致口腔癌的分子病理学分析

基本信息

批准号：
15256005
负责人：
SAKU Takashi
金额：
$ 21.8万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15256005/
关键词：
Asia oral cancer carcinoma in-situ epithelial dysplasia submucosal fibrosis extracellu matrix chewing tobacco pathological epidemiology 口腔がん噛みたばこ表在型扁平上皮癌前癌病変 OSF 歯科補綴物

项目摘要

Oral cancers and its precancerous lesions were collected from Taiwan, India, Sri-Lanka, Bangladesh, Yemen, Madagascar, and Myanmar. Through the present collection of oral cancers and precancerous lesions, we have found lesions referred to as superficial carcinoma with or without the custom of chewing tobacco. The frequencies of oral carcinoma were shown to be related to chewing habits. The clinicopathological summary of superficial carcinoma in Japan was characterized by elder female patients, more commonly occurring in the tongue and gingival, less consumptions of tobacco for smoking and alcohol, but association with prosthetic treatments. In contrast, the lesion from Asian countries was found exclusively in the buccal mucosa and gingival, and the patients were mainly males with chewing habits. Histopathology of the superficial carcinoma of the Japanese and Asian patients resembled each other. They were commonly composed of carcinoma in-situ, which could be divided into three types, s … More uch as basaloid, verrucous, and acanthotic, and of surrounding epithelial dysplasia with the characteristic two-phase appearances. In addition, intraepithelial deposition of perlecan was demonstrated in epithelial dysplasia and carcinoma in-situ. This finding has been developed into a new concept of intraepithelial stroma. These two findings had greatly contributed to an objective histopathlogical diagnosis for oral borderline malignancies.Using paraffin-embedded specimens collected from Asian countries, oral submucous fibrosis and superficial carcinomas were investigated in by immunohistochemistry and in-situ hybridization, PCR, and DNA sequencing techniques. Histopathologically, oral submucous fibrosis was graded with immunohistochemical patterns of extracellular matrix remodeling. The final status of oral submucous fibrosis was also shown to be poorly vascularized or hypoxic, which were important background for oral carcinogenesis. DNA samples obtained by microdissection were analyzed for mutational events in cancer-related genes. Among them, there were several characteristic mutations in the p53 gene which were shared by the collected cases, although samples from Asian countries were not always appropriate for DNA extraction and following experiments.Samples of chewing staffs, such as betel, areca nuts, or qat, were organic-chemically demonstrated to have basically the same ingredients from area to area.The data obtained in this study showed that oral carcinomas caused by different environmental factors shared similar genetic alterations and histopathological characteristics. Less

口腔癌及其癌前病变收集自台湾、印度、斯里兰卡、孟加拉国、也门、马达加斯加和缅甸。通过目前收集的口腔癌和癌前病变，我们发现了被称为浅表癌的病变，有或没有。口腔癌的发病率与咀嚼习惯有关。日本浅表癌的临床病理特点是女性患者年龄较大，多见于舌和牙龈，食用量较少。烟草与吸烟和饮酒有关，但与修复治疗有关。相比之下，亚洲国家的病变仅发现于颊粘膜和牙龈，并且患者主要是具有咀嚼习惯的日本人和日本人的浅表癌。亚洲患者多为原位癌，可分为基底样癌、疣状癌、棘皮样癌和周围上皮癌三种类型。此外，在上皮不典型增生和原位癌中也证实了基底膜蛋白内沉积，这一发现已发展为上皮内基质的新概念，这两个发现极大地促进了客观的组织病理学。口腔交界性恶性肿瘤的诊断。使用从亚洲国家收集的石蜡包埋标本，研究了口腔粘膜下纤维化和浅表癌免疫组织化学和原位杂交、PCR和DNA测序技术通过细胞外基质重塑的免疫组织化学模式对口腔粘膜下纤维化进行分级，口腔粘膜下纤维化的最终状态也显示为血管化不良或缺氧，这是重要的背景。对通过显微切割获得的DNA样本进行了癌症相关基因的突变事件分析，其中存在几个特征性突变。尽管来自亚洲国家的样本并不总是适合 DNA 提取和后续实验，但收集到的病例共有 p53 基因。咀嚼棒的样本，如槟榔、槟榔或咖特，经有机化学证明基本上具有不同地区的成分相同。本研究获得的数据表明，不同环境因素引起的口腔癌具有相似的遗传改变和组织病理学特征。