Direct Involvement of Epstein-Barr Virus in Adenocarcinoma of the Lung

EB病毒感染在肺腺癌腫瘤細胞的直接證據

施志勳(Chih-Shiun Shih) ； 許南榮(Nan-Yung Hsu) ； 周寬基(Kuan-Chih Chow) ； 林智一(Tze-Yi Lin)

《Mid-Taiwan Journal of Medicine》 6卷2期 (2001/06) Pp. 101-104

https://doi.org/10.6558/MTJM.2001.6(2).6

摘要

EB病毒感染與惡性腫瘤之間的因果關係，自從在鼻咽癌的研究被提出及重視之後，相關的論文報告即不勝枚舉。在肺癌中，絕大多數的數據卻都指向與肺原發性淋巴上皮瘤樣腫瘤(Primary lymphoepithelioma-like carcinoma of the lung)有高度相關。此次，我們報告這一個56歲女性肺腺癌病例，即是少數有直接證據可以充分顯示EB病毒染與肺腺癌腫瘤細胞之間可能的密切關係。首先，我們在這位接受手術切除的肺腺癌病人的腫瘤切片上以原位雜交(in situ hybridization)及聚合?鏈反應(polymerase chain reaction)等分子生物技術來偵測EB病毒的存在。再者，我們在肺腺癌的腫瘤細胞襄找到EB病毒專屬之擴散型的早期抗原(early antigen diffused， EA-D)以及潛伏期細胞膜蛋白質(latent membrane protein， LMP-l) ，更可以加強EB病毒在腫瘤細胞中的染證據。最後，有趣的是，在我們分別從肺靜脈、肺動脈和週邊血管收集血液，並用酵素免疫測定法(enzyme-linked immunosorbent assay， ELISA)檢測血清中EB病 毒的免疫球蛋白A(IgA)濃度中，結果發現，從腫瘤細胞周圍引流的肺靜脈，其血清中IgA 的濃度比動脈血和周邊血有統計意義的高。顯示免疫球蛋白有可能由腫瘤細胞所分泌。我們提出這個文獻上少見的EB病毒感染與肺腺癌腫瘤相關的病例報告，並以充分的分子物學上的實驗室數據來佐證，顯示EB病毒感染在腫瘤發生學上的另一個研究方向。

關鍵字

肺腺癌 ； EB病毒

並列摘要

In order to determine the relationship between Epstein-Barr virus infection and adenocarcinoma of the lung, we applied in situ hybridization and polymerase chain reaction to examine a surgical specimen from a Taiwanese patient with lung adenocarcinoma. The association between EBV infection and tumor biology was evaluated by ISH and immunoperoxidase methods in order to detect EBV latent membrane protein, early antigen diffused, and EBV BZLF-I replication activator. Expressions of EBER were detected in adenocarcinoma tumor cells by ISH. The presence of EBV in the cancer cells was further confirmed by PCR. Interestingly, the serum level of IgA to EBNA-l and EA-D antigens in the pulmonary vein determined by an enzyme-linked immunosorbent assay was higher than that in the pulmonary artery or peripheral blood. Cell-free EBV DNA determined by semi-quantitative that from the peripheral blood or pulmonary artery. These data indicate that viral gene expression in this patient was a mixture of latent and activated infection, suggesting that IgA might be produced near the tumor nest.

並列關鍵字

lung adenocarcinoma ； Epstein-Barr virus