Rennspiess Dorit, Pujari Sreedhar, Keijzers Marlies, Abdul-Hamid Myrurgia A, Hochstenbag Monique, Dingemans Anne-Marie, Kurz Anna Kordelia, Speel Ernst-Jan, Haugg Anke, Pastrana Diana V, Buck Christopher B, De Baets Marc H, Zur Hausen Axel
Departments of *Pathology, †Cardiothoracic Surgery, and ‡Pulmonology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; §Department of Internal Medicine IV, University Hospital Aachen, Aachen, Germany; ║Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland; and ¶Department of Neuroscience, Maastricht University, School of Mental Health and Neuroscience (MHeNS), Maastricht, The Netherlands.
J Thorac Oncol. 2015 Feb;10(2):360-6. doi: 10.1097/JTO.0000000000000390.
Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Because murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors.
HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-polymerase chain reaction (PCR), and immunohistochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested.
HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC, large T antigen expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. Of the 20 hyperplastic thymi, 40% were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative.
The presence of HPyV7-DNA and large T antigen expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG.
尽管对可能构成人类胸腺瘤发病机制基础的分子遗传学进行了广泛研究,但其病因仍知之甚少。由于鼠多瘤病毒可在小鼠中持续诱发胸腺瘤,我们评估了新型人类多瘤病毒7(HPyV7)在人类胸腺上皮肿瘤中的存在情况。
对37例胸腺瘤进行了HPyV7-DNA荧光原位杂交(FISH)、DNA聚合酶链反应(PCR)和免疫组织化学(IHC)检测。其中,26例先前被诊断为重症肌无力(MG)。此外,还检测了20例胸腺增生组织和20例胎儿胸腺组织。
HPyV7-FISH显示23例胸腺瘤(62.2%)的肿瘤上皮细胞内有特异性核杂交信号。除了一些例外情况,HPyV7-FISH数据与HPyV7-DNA PCR结果相关。通过IHC检测到HPyV7大T抗原表达,双重染色证实其在肿瘤上皮细胞中的表达。26例MG阳性胸腺瘤中有18例以及11例MG阴性胸腺瘤中有7例为HPyV7阳性。在20例增生性胸腺中,40%通过PCR检测为HPyV7阳性,FISH和IHC在滤泡淋巴细胞中证实了这一结果。所有检测的20例胎儿胸腺均为HPyV7阴性。
大多数胸腺瘤中存在HPyV7-DNA和大T抗原表达,这可能将HPyV7与人类胸腺瘤的发生联系起来。需要进一步研究以阐明HPyV7与MG之间可能的关联。