Chen F F, Yan J J, Lai W W, Jin Y T, Su I J
Department of Pathology, National Cheng Kung University Medical Center, Tainan, Taiwan.
Cancer. 1998 Jun 15;82(12):2334-42. doi: 10.1002/(sici)1097-0142(19980615)82:12<2334::aid-cncr6>3.0.co;2-s.
Epstein-Barr virus (EBV) infection in nonsmall cell lung carcinoma (NSCLC) has been demonstrated in some ethnic groups. The pathobiology and the role of EBV and oncoprotein expression in these tumors have not been studied extensively. In this study, the authors investigated EBV-encoded RNA-1 (EBER1) transcripts by in situ hybridization and the expression of latent membrane protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry in NSCLC patients from Taiwan, where nasopharyngeal carcinoma is endemic.
A total of 127 cases of NSCLC (43 cases of squamous cell carcinoma [SCC], 67 cases of adenocarcinoma [AD], 12 cases of large cell carcinoma [LCC], and 5 cases of lymphoepithelioma-like carcinoma [LE]) were included. A sensitive polymerase chain reaction-derived, digoxigenin-labeled DNA probe for in situ detection of EBER1 transcripts was performed for the detection of EBV. Immunohistochemistry using the avidin-biotin-immunoperoxidase method was also performed to evaluate the expression of bcl-2 and LMP-1.
EBER1 was detected in 11 of the 127 NSCLC cases (8.7%; 6 SCC cases and 5 LE cases). All 5 LE cases were EBV-positive, whereas only 6 of the 43 SCC cases (14%), 0 of 67 AD cases, and 12 LCC cases were EBV-positive (P < 0.05). All five LE cases showed diffuse, strong, positive staining of tumor cells; five of the six SCC cases showed diffuse but weak staining. Among the nontumor epithelial cells, there was no EBER1 staining of any of the 11 EBER1-positive cases. The mean age of the LE patients was 10 years younger than that of the patients with other histological types. All 5 LE patients were nonsmokers, whereas 3 of the 6 patients with EBER1-positive SCC (50%) were smokers. EBER1 expression did not correlate with the 2-year survival rate of overall cases, but all 5 LE patients were alive without clinical evidence of disease at last follow-up. Gender, lymph node or distant metastasis, and clinical stage were not found to have any correlation with EBER1 expression (P > 0.05). All LE cases had bcl-2 oncoprotein expression (100%). This frequency was significantly different from other histologic types (P < 0.05). The LMP-1 detection rate was low and demonstrated no correlation with bcl-2 expression.
In this study, the authors found that the primary LE of the lung is associated with young age, a history of not smoking, high bcl-2 immunoreactivity, and better survival rate. These characteristics demonstrate that EBV-associated LE of the lung is a unique entity. The findings of the current study suggest that EBV infection may play a different role in the tumorigenesis of primary LE of the lung than it does in other EBER1-positive NSCLCs.
在一些种族群体中已证实非小细胞肺癌（NSCLC）存在爱泼斯坦-巴尔病毒（EBV）感染。EBV的病理生物学及其在这些肿瘤中的作用以及癌蛋白表达尚未得到广泛研究。在本研究中，作者通过原位杂交研究了台湾地区NSCLC患者中EBV编码的RNA-1（EBER1）转录本，并通过免疫组织化学研究了潜伏膜蛋白-1（LMP-1）和bcl-2蛋白的表达，台湾地区是鼻咽癌的高发地区。
共纳入127例NSCLC患者（43例鳞状细胞癌[SCC]、67例腺癌[AD]、12例大细胞癌[LCC]和5例淋巴上皮瘤样癌[LE]）。采用一种敏感的聚合酶链反应衍生的、地高辛标记的DNA探针进行原位检测EBER1转录本，以检测EBV。还采用抗生物素蛋白-生物素-免疫过氧化物酶法进行免疫组织化学，以评估bcl-2和LMP-1的表达。
127例NSCLC患者中有11例检测到EBER1（8.7%；6例SCC患者和5例LE患者）。所有5例LE患者均为EBV阳性，而43例SCC患者中仅6例（14%）、67例AD患者中0例以及12例LCC患者中1例为EBV阳性（P<0.05）。所有5例LE患者的肿瘤细胞均呈弥漫性、强阳性染色；6例SCC患者中有5例呈弥漫性但弱阳性染色。在非肿瘤上皮细胞中，11例EBER1阳性病例均未出现EBER1染色。LE患者的平均年龄比其他组织学类型的患者小10岁。所有5例LE患者均不吸烟，而6例EBER1阳性SCC患者中有3例（50%）吸烟。EBER1表达与所有病例的2年生存率无关，但所有5例LE患者在最后一次随访时均存活且无疾病临床证据。未发现性别、淋巴结或远处转移以及临床分期与EBER1表达有任何相关性（P>0.05）。所有LE病例均有bcl-2癌蛋白表达（100%）。该频率与其他组织学类型有显著差异（P<0.05）。LMP-1检测率较低，且与bcl-2表达无相关性。
在本研究中，作者发现原发性肺LE与年轻、无吸烟史、高bcl-2免疫反应性和更好的生存率相关。这些特征表明肺EBV相关LE是一种独特的实体。本研究结果表明，EBV感染在原发性肺LE的肿瘤发生中可能发挥与其他EBER1阳性NSCLC不同的作用。
