鼻咽癌变过程生物学特性研究的进展

作者总结所在研究小组近5年来在鼻咽癌变过程生物学特性研究方面的主要成果。结合国内外这一领域的进展,提出作者对鼻咽癌变机理的看法,为了研究鼻咽癌变,本课题组对20000多例鼻咽癌活检和600多例EB病毒血清学阳性并已随访12年以上的鼻咽活检材料,进行了除组织病理学染色外,还采用动物实验,分子生物学方法（如原位杂交和PCR等）的研究,至今,完成论文26篇,并正式发表在国内外医学生物学杂志上,综合得到的结论是：（1）鼻咽癌变过程中所见的形态发生学顺序为鳞状化生,上皮异型性变,原位癌和微小浸润癌。（2）这种形态发生学顺序常可见于鼻咽粘膜上皮的一定范围,因此鼻咽癌变是一种区域性癌变。（3）EB病毒DNA和小RNAs在上皮呈异型性变时即可被检测到,且若干病毒基因编码产物,特别是LMP1,可在异型上皮,原位癌和微小浸润癌中表达,因此EB病毒在鼻咽癌变过程中可能起着关键的作用。（4）EB病毒基因编码产物与上皮细胞内,由逐步变异的调节细胞周期相关基因异常表达产物间的相互作用,构成了鼻咽癌变过程中的一系列分子 事件。（5）由于EB病毒特异性细胞毒性T淋巴细胞不但可在癌巢中观察到,且可在周围血液中检测到,因此个体的细胞免疫状态也是影响鼻咽癌变的重要因素。

Advancement of studying the biological characteristics of nasopharyngeal carcinogenesis

This review is to summarize the main achievements of studying the biological characteristics of nasopharyngeal carcinogenesis performed by the authors' research team and the recent advancement in this field during the past 5 years as well as to explain the authors' viewpoints concerning the nasopharyngeal carcinogenesis. In order to study the nasopharyngeal carcinogenesis, more than 20,000 nasopharyngeal carcinoma biopsies and more than 600 nasopharyngeal biopsies of Epstein-Barr virus seropositive persons who had been got follow-up over 12 years, were collected. In addition, nude mice and cell lines were also to be utilized. Besides histopathological staining, methods of molecular biology, including in-situ hybridization, PCR etc. were applied. Up to date, 26 papers concerning this subject had been formally published in the medico-biological journals at home and abroad. The results and conclusions were as follows. (1) The squamous metaplasia, epithelial dysplasia, carcinoma in-situ and microinvasive carcinoma are the morphogenetic sequence found in nasopharyngeal carcinogenesis. (2) This morphogenetic sequence is frequently observed in a restricted area of nasopharyngeal mucosal epithelium, representing as an appearance of field carcinogenesis. (3) EB virus may play a critical role in nasopharyngeal carcinogenesis, since EB virus DNA and small RNAs could be detected in epithelial dysplasia first and several viral encoded products, especially LMP1, might be expressed in dysplasia, carcinoma in-situ and microinvasive carcinoma. (4) The multigenic mechanisms, including interactions between EB viral genes encoded products and the products abnormally expressed step by step from genes related to cell-cycle regulation, are the molecular events involved in nasopharyngeal carcinogenesis. (5) The cellular immunity of individuals should also be considered as an important factor influencing nasopharyngeal carcinogenesis, because EB virus specific cytotoxic T-lymphocytes could not only be observed in carcinoma nests but also detected in peripheral blood.