Lau Sean K, Chen Yuan-Yuan, Berry Gerald J, Yousem Samuel A, Weiss Lawrence M
Department of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.
Mod Pathol. 2003 Dec;16(12):1242-7. doi: 10.1097/01.MP.0000097363.72401.00.
Epstein-Barr virus has been linked to an increasing number of nonhematolymphoid conditions. Epstein-Barr virus was recently described in association with fibroadenomas of the breast occurring in immunosuppressed patients. To further investigate the potential association of Epstein-Barr virus with fibroadenoma in the context of immune dysfunction, 11 cases of fibroadenoma of the breast in immunosuppressed organ transplant recipients were examined. Cases were evaluated for the presence of Epstein-Barr virus by polymerase chain reaction, in situ hybridization, and immunohistochemical methods. The presence of Epstein-Barr virus genomic DNA was studied by polymerase chain reaction amplification using primers flanking the BamHI-W fragment of the Epstein-Barr virus genome, as well as the Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes. Cases were also evaluated for the presence of defective heterogeneous Epstein-Barr virus DNA. In addition, morphologic analysis by in situ hybridization for Epstein-Barr virus-encoded RNA-1 and immunohistochemistry for latent membrane protein-1 were performed. Epstein-Barr virus DNA was detected in 4 of 11 (36%) cases with BamHI-W polymerase chain reaction. Polymerase chain reaction studies for Epstein-Barr virus nuclear antigen-4 and latent membrane protein-1 genes were positive in two and four cases, respectively. No defective Epstein-Barr virus genomes were identified in any of the cases. Quantitative polymerase chain reaction demonstrated low levels of Epstein-Barr virus in the fibroadenomas studied. Despite the detection of Epstein-Barr virus genomes in a subset of the cases examined, the constituent epithelial and stromal components of all fibroadenomas demonstrated no evidence of Epstein-Barr virus-encoded RNA-1 by in situ hybridization or latent membrane protein-1 expression by immunohistochemistry. Rare Epstein-Barr virus-encoded RNA-1-positive lymphocytes were observed in some cases, which may account for the positive polymerase chain reaction results. The findings of the present study argue against a significant relationship between Epstein-Barr virus and fibroadenomas of the breast in the setting of transplant-associated immunosuppression.
爱泼斯坦-巴尔病毒与越来越多的非血液淋巴系统疾病有关。最近有报道称,爱泼斯坦-巴尔病毒与免疫抑制患者发生的乳腺纤维腺瘤有关。为了在免疫功能障碍的背景下进一步研究爱泼斯坦-巴尔病毒与纤维腺瘤之间的潜在关联,对11例免疫抑制器官移植受者的乳腺纤维腺瘤进行了检查。通过聚合酶链反应、原位杂交和免疫组化方法评估病例中爱泼斯坦-巴尔病毒的存在情况。使用位于爱泼斯坦-巴尔病毒基因组BamHI-W片段侧翼的引物,以及爱泼斯坦-巴尔病毒核抗原-4和潜伏膜蛋白-1基因,通过聚合酶链反应扩增研究爱泼斯坦-巴尔病毒基因组DNA的存在情况。还评估了病例中是否存在缺陷性异质性爱泼斯坦-巴尔病毒DNA。此外,通过原位杂交检测爱泼斯坦-巴尔病毒编码的RNA-1进行形态学分析,并对潜伏膜蛋白-1进行免疫组化。11例中有4例(36%)通过BamHI-W聚合酶链反应检测到爱泼斯坦-巴尔病毒DNA。爱泼斯坦-巴尔病毒核抗原-4和潜伏膜蛋白-1基因的聚合酶链反应研究分别在2例和4例中呈阳性。所有病例均未鉴定出缺陷性爱泼斯坦-巴尔病毒基因组。定量聚合酶链反应显示,所研究的纤维腺瘤中爱泼斯坦-巴尔病毒水平较低。尽管在所检查的部分病例中检测到了爱泼斯坦-巴尔病毒基因组,但所有纤维腺瘤的组成上皮和间质成分通过原位杂交均未显示有爱泼斯坦-巴尔病毒编码的RNA-1证据,通过免疫组化也未显示有潜伏膜蛋白-1表达。在一些病例中观察到罕见的爱泼斯坦-巴尔病毒编码的RNA-1阳性淋巴细胞,这可能是聚合酶链反应结果呈阳性的原因。本研究结果表明,在移植相关免疫抑制的情况下,爱泼斯坦-巴尔病毒与乳腺纤维腺瘤之间不存在显著关系。