鼻咽癌形态发生学的EB病毒感染研究

Study of Epstein-Barr Virus infection in Nasopharyngeal Morphological Carcinogenesis

目的 探讨EB病毒在鼻咽癌形态发生学的哪一阶段进入鼻咽上皮细胞。方法 从3212例 鼻咽癌活检组织切片中筛选并收集到具有各种癌旁上皮病变的鼻咽癌标本85例,用核酸原位杂交 法检测癌旁上皮病变中EB病毒编码的小RNAs(EBERs)感染,其中31例具有癌旁鳞状化生病变的鼻 咽癌组织进一步用核酸原位杂交法检测EB病毒溶解期产物EA-D(early antigen-diffuse)mRNA。 结果 85例鼻咽癌标本共观察到154个癌旁上皮病变病灶:39个柱状上皮单纯增生灶、43个化生 鳞状上皮增生灶、41个上皮异型性变(轻度、中度和重度)灶、17个原位癌灶及14个微小浸润癌 灶。所有癌旁正常或单纯增生的柱状上皮、化生鳞状上皮均显示EBERs阴性。一部分(11/41,26. 83％)癌旁异型性变上皮中的少数细胞表达EBERs,大部分原位癌(12/17,70.59%)及全部微小浸润 癌都显示相当数量的EBERs阳性癌细胞。31例可见癌旁鳞状化生上皮病变的鼻咽癌中有10例癌旁 上皮角化细胞的细胞核上显示出EA-D mRNA阳性信号。结论 EB病毒可以首先感染异型性变的上 皮细胞,然后可能与其他致癌产物协同对鼻咽癌变过程起了重要的作用。此外,从鼻咽癌细胞中释 出的EB病毒可以重复感染癌旁鳞状化生上皮内的角化细胞,这种溶解性感染不具有重要的病理学 意义。

Objective At what phase of morphogenetic sequence (squamous metaplasia, epithelial dysplasia, carcinoma in situ and microinvasive carcinoma), the EBV infects the epithelial cells initially is the critical issue for understanding the role of EBV playing in nasopharyngeal carcinogenesis. In order to answer this question, the following investigation was done. Methods 85 NPC biopsy sections having paratumourous epithelial lesion suitable for this investigation from 3,212 NPCs were collected, and were stained with EBERs in situ hybridization. EA-D (early antigen-diffuse) mRNA in situ hybridization had been performed in 31 NPC sections having paratumourous metaplas-tic squamous epithelium. Results 154 epithelial lesions were collected in that of 85 NPCs. There were 39 foci of simply hyperplastic columnar epithelium, 43 foci of metaplastic squamous epithelium, 41 dysplastic epithelial lesions, 17 carcinoma in situ and 14 microinvasive carcinoma lesions. All of the normal or simply hyperplastic columnar (39/39) and metaplastic squamous epithelium (43/43) was EBERs-negative. A portion of the dysplastic epithelial lesions (11/41, 26.83%) had a few EBERs-positive epithelial cells found. Most of the carcinoma in situ and all microinvasive carcinoma lesions contained a considerable number of EBERs-positive neoplastic cells (12/17, 70. 59% and 14/14,100%, respectively). The EA-D mRNA signals could be found within nuclei of a few keratinocytes in 10 specimens. That is to say, the keratinocytes located at the superior layers of metaplastic squamous epithelium could be partially infected with lytic infection of EBV. Conlusions This observation clearly illustrates that EBV could infect the dysplastic epithelial cells first and might interact with other oncogenic products to play an important role in nasopharyngeal carcinogenesis. On another aspect, the EBV released from the NPC cells could superinfect the neighboring keratinocytes of paratumourous squamous epithelium and has no pathognomonic significance