Cingolani A, Gastaldi R, Fassone L, Pierconti F, Giancola M L, Martini M, De Luca A, Ammassari A, Mazzone C, Pescarmona E, Gaidano G, Larocca L M, Antinori A
Department of Infectious Diseases, Catholic University.
J Clin Oncol. 2000 Oct 1;18(19):3325-30. doi: 10.1200/JCO.2000.18.19.3325.
This study aimed at correlating Epstein-Barr virus (EBV) infection of systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the development of a CNS localization of the tumor.
Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients included in the study (n = 50). Pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1-specific primers. In addition, selected EBV-positive lymphomas were subjected to a detailed characterization of EBV molecular heterogeneity.
Eleven patients had a CNS involvement at some point during their clinical history (four at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and 19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors significantly predictive of CNS involvement were EBV infection of the tumor (P=.003), an extranodal disease at diagnosis other than CNS (P=.006), and a non-CNS relapse (P=.01). In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days.
These results show that EBV infection of the tumor clone significantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors.
本研究旨在探讨系统性艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）的爱泼斯坦-巴尔病毒（EBV）感染与肿瘤中枢神经系统（CNS）定位发展之间的相关性。
收集了本研究纳入的所有系统性AIDS-NHL患者（n = 50）的人口统计学、流行病学、临床、组织学和病毒学特征。病理标本根据NHL的工作分类法和修订的欧美淋巴瘤分类法进行分类。通过EBV小编码RNA原位杂交研究肿瘤组织样本中的EBV感染；使用爱泼斯坦-巴尔核抗原-1特异性引物，通过巢式聚合酶链反应检测脑脊液中的EBV-DNA。此外，对选定的EBV阳性淋巴瘤进行EBV分子异质性的详细表征。
11例患者在其临床病程中的某些时候出现CNS受累（4例在诊断时，7例在复发时）。30例患者（11例有CNS受累，19例无）肿瘤存在EBV感染。脑脊液中EBV-DNA检测对淋巴瘤CNS受累的敏感性、特异性、阳性预测值和阴性预测值分别为90%、100%、100%和97.6%。显著预测CNS受累的因素为肿瘤的EBV感染（P = 0.003）、诊断时除CNS外的结外疾病（P = 0.006）和非CNS复发（P = 0.01）。在4例CNS受累病例中，脑脊液中的EBV-DNA比任何其他疾病迹象平均提前35天出现。
这些结果表明，肿瘤克隆的EBV感染显著增加了系统性AIDS-NHL发生CNS受累的风险，而不考虑特定的分子特征。在AIDS-NHL患者的脑脊液中检测EBV-DNA可能筛选出CNS受累风险较高的病例，因此可能在这些肿瘤的治疗分层中证明有用。
