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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来自台湾、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性癌的病变，无论是否有咀嚼烟草的习惯。口腔癌的发生率与咀嚼习惯有关。日本浅表性癌的临床病理特点是年龄较大的女性患者，多发生在舌部和牙龈，吸烟和饮酒的烟草消耗量较少，但与假体治疗有关。相比之下，来自亚洲国家的病变仅发现于颊粘膜和牙龈，患者主要是有咀嚼习惯的男性。日本人和亚洲人的浅表性癌的组织病理学表现相似。通常由原位癌组成，可分为三种类型，S…更多的表现为基底样、疣状和棘皮样，以及周围的上皮异常增生症，具有典型的双期表现。此外，在上皮不典型增生和原位癌中发现了Perlecan在上皮内的沉积。这一发现已经发展成为上皮内间质的新概念。利用从亚洲国家采集的石蜡包埋标本，采用免疫组织化学、原位杂交、聚合酶链式反应和DNA测序技术，对口腔粘膜下纤维性变和浅表性癌进行了研究。组织病理学上，口腔粘膜下纤维化以细胞外基质重塑的免疫组织化学模式进行分级。口腔粘膜下纤维化的最终状态也被显示为低血管或低氧，这是口腔癌发生的重要背景。通过显微切割获得的DNA样本被分析了癌症相关基因的突变事件。其中，虽然来自亚洲国家的样本并不总是适合于DNA提取和后续实验，但其中有几个特征突变是收集的病例所共有的。从有机化学角度证明，槟榔、槟榔或卡塔尔等咀嚼人员的样本具有基本相同的成分。本研究获得的数据表明，由不同环境因素引起的口腔癌具有相似的遗传变化和组织病理学特征。较少