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

从台湾、印度、斯里兰卡、孟加拉国、也门、马达加斯加和缅甸收集口腔癌及其癌前病变。通过目前收集的口腔癌和癌前病变，我们发现病变被称为浅表癌有或没有咀嚼烟草的习俗。口腔癌的发生率与咀嚼习惯有关。日本浅表癌的临床病理学总结特征为老年女性患者，更常见于舌和牙龈，吸烟和饮酒较少，但与假体治疗相关。相反，亚洲国家的病变仅见于颊粘膜和牙龈，患者主要为有咀嚼习惯的男性。日本和亚洲患者浅表癌的组织学相似。以原位癌多见，可分为三型， ...更多信息 例如基底样、疣状和棘皮样，以及具有特征性双相外观的周围上皮发育不良。此外，在上皮不典型增生和原位癌中也发现了串珠素的上皮内沉积。这一发现已经发展成为上皮内基质的新概念。本研究采用免疫组化、原位杂交、PCR和DNA测序技术，对亚洲国家口腔粘膜下纤维化和浅表癌的石蜡包埋标本进行了研究。组织学上，口腔粘膜下纤维化分级与细胞外基质重塑的免疫组化模式。口腔粘膜下纤维性变的最终状态也显示为血管化不良或缺氧，这是口腔癌发生的重要背景。通过显微切割获得的DNA样品分析癌症相关基因的突变事件。其中，p53基因中有几个特征性突变，这些突变与所收集的病例相同，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。咀嚼棒的样本，如槟榔、槟榔或咖特，是有机的-从化学上看，不同地区的口腔癌具有基本相同的成分。本研究获得的数据表明，不同的环境因素具有相似的遗传改变和组织病理学特征。少

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