鼻咽癌淋巴结转移组织中EB病毒BamH Ⅰ“f”变异分析

Analysis of Epstein-Barr virus BamH Ⅰ ＂f＂ variant in nodal metastasis of nasopharyngeal carcinoma

目的探讨高发区原发鼻咽癌及相应的淋巴结转移癌组织中EB病毒BamH Ⅰ“f”变异情况。方法原位杂交法检测了21对鼻咽原发癌及其相应的淋巴结转移癌组织、22例未伴淋巴结转移的鼻咽癌组织中EB病毒EBER的表达，进而采用PCR和限制性酶切分析技术检测了所有鼻咽癌病例及相应的淋巴结转移癌组织和50例鼻咽黏膜慢性炎组织中EB病毒BamH Ⅰ“f”变异情况。结果所有鼻咽癌和相应的淋巴结转移癌组织均呈EBER阳性表达。21对鼻咽原发癌及其相应的淋巴结转移癌组织、22例未伴淋巴结转移的鼻咽癌组织和50例鼻咽黏膜慢性炎组织中EB病毒BamH Ⅰ“f”基因变异率分别为52．4％（11／21）、57．1％（12／21）、81．8％（18／22）和2．1％（1／47）。统计学分析显示，鼻咽癌组织“f”变异率明显高于鼻咽黏膜慢性炎组织的变异率；伴淋巴结转移的鼻咽癌组织中“f”变异率并不比未伴淋巴结转移的鼻咽癌组织的变异率高。另外，表现为“f”变异的1例鼻咽黏膜慢性炎呈“F／f”型，且其组织学可见部分鼻咽上皮出现轻度的不典型增生。结论高发区鼻咽癌组织中EB病毒BamH Ⅰ“f”变异率远高于同一地区鼻咽黏膜慢性炎组织中的变异率；鼻咽癌淋巴结转移组织中也有较高的BamH Ⅰ“f”变异率，且与其原发癌组织基本一致。

Objective To investigate the Epstein-Barr virus （EBV） BamH Ⅰ ＂f＂ variant in primary nasopharyngeal carcinoma （NPC） and its metastases in lymph nodes （LN）. Methods In situ hybridization was used to detect EBV-encoded small RNA （EBER） expression in 21 paired paraffinembedded tissue from primary NPC and their lymph node metastases and 22 primary NPC without lymph node metastasis. PCR and restriction fragment length polymorphism （RFLP） assay were used to detect EBV BamH Ⅰ ＂f＂ variant in all cases of NPCs, lymph node metastases and 50 cases of chronic inflammation of nasopharynx from Canton. Results All cases of NPCs and their lymph node metastases showed EBER expression, indicating a high EBV-positive rate in Cantonese NPC patients. EBV BamH Ⅰ ＂f＂ variant was found in 11 cases （52. 4%, 11/21 ） of primary NPCs with LN metastasis, 12 cases （57. 1%, 12/21 ） of the LN metastases, and 18 cases （81.8%, 18/22） of primary NPCs without LN metastasis. However, of the 50 cases of chronic inflammation of nasopharynx, only one case （2. 1%, 1/47） demonstrated BamH Ⅰ ＂f＂ variant. The frequency of BamH Ⅰ ＂f＂ variant in NPC was therefore dramatically higher than that in chronic inflammation of nasopharynx. It is of note that atypical hyperplasia was observed in a few epithelial cells from the case of chronic inflammation of nasopharynx expressing BamH Ⅰ ＂f＂ variant. Conclusions The frequency of EBV BamH Ⅰ ＂f＂ variant in NPC is significantly higher than that in chronic inflammation of nasopharynx. It is the first demonstration that the BamH Ⅰ ＂f＂ variant is also present in the LN metastases of NPC. The frequency of BamH Ⅰ ＂f＂ variant in metastatic NPC of the lymph node is almost equal to that of primary NPCs.