Zhao Li, Ding Jian-Yong, Tao Yun-Lan, Zhu Kun, Chen Gang
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Infect Agent Cancer. 2023 Jun 9;18(1):37. doi: 10.1186/s13027-023-00497-9.
Epstein-Barr virus (EBV) is well known to be associated with a lot of tumors, including lymphoma, nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and some other carcinomas with similar lymphoepithelioma-like features. However, the association between EBV and thymic epithelial tumors (TETs) is inconclusive as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. The geographical difference of the patients is also one of the reasons for the different points of view.
In our study, we examined 72 thymomas, including 3 cases of type A thymomas, 27 cases of type AB, 6 cases of type B1, 26 cases of type B2 and 10 cases of type B3 thymomas, and 15 thymic carcinomas to detect the viral genome at both DNA and RNA levels. The genome DNA of fresh tissues was first screened by nested polymerase chain reaction (PCR), which could be regarded as the most sensitive method to detect small amounts of DNA. Then all the tissue blocks were further submitted for viral localization by Epstein-Barr-encoded RNA (EBER) ISH. Group parameters were assessed using the chi-square test at a significance level of p < 0.05.
Nested PCR results showed that none of type A, eight (29.6%) type AB, one (16.7%) type B1, fifteen (57.7%) type B2, and four (40.0%) type B3 were positive for EBV genome. However, none of them detected EBER expression except for one case of type B2 thymoma. Fourteen (93.3%) thymic carcinomas were positive for EBV by nested PCR, of which three displayed weak nuclear signals within the tumor cells by EBER ISH.
These results showed that nested PCR was a sensitive method for screening the EBV genome in thymic epithelial tumors. As the malignancy of thymoma increases, the rate of EBV infection became higher. Thymic carcinomas were well associated with the Epstein-Barr virus.There was significant association between the EBV infection rate and thymoma type (p < 0.05). We further analyzed the association between EBV infection and myasthenia gravis. However, it showed no significant difference(p = 0.2754), although the EBV infection rate was higher in the thymomas with myasthenia gravis.
众所周知，爱泼斯坦-巴尔病毒（EBV）与许多肿瘤相关，包括淋巴瘤、鼻咽癌、EBV相关胃癌以及其他一些具有类似淋巴上皮瘤样特征的癌。然而，EBV与胸腺上皮肿瘤（TETs）之间的关联尚无定论，因为这方面的报道并不完全一致，且所采用的方法具有不同的敏感性和特异性。患者的地域差异也是观点不同的原因之一。
在我们的研究中，我们检查了72例胸腺瘤，包括3例A型胸腺瘤、27例AB型、6例B1型、26例B2型和10例B3型胸腺瘤，以及15例胸腺癌，以在DNA和RNA水平检测病毒基因组。新鲜组织的基因组DNA首先通过巢式聚合酶链反应（PCR）进行筛查，这可被视为检测少量DNA的最敏感方法。然后，所有组织块进一步通过爱泼斯坦-巴尔编码RNA（EBER）原位杂交进行病毒定位。使用卡方检验评估组参数，显著性水平为p < 0.05。
巢式PCR结果显示，A型胸腺瘤均为阴性，AB型中有8例（29.6%）、B1型中有1例（16.7%）、B2型中有15例（57.7%）、B3型中有4例（40.0%）EBV基因组呈阳性。然而，除1例B2型胸腺瘤外，其余均未检测到EBER表达。14例（93.3%）胸腺癌通过巢式PCR检测EBV呈阳性，其中3例通过EBER原位杂交在肿瘤细胞内显示弱核信号。
这些结果表明，巢式PCR是筛查胸腺上皮肿瘤中EBV基因组的敏感方法。随着胸腺瘤恶性程度的增加，EBV感染率升高。胸腺癌与爱泼斯坦-巴尔病毒密切相关。EBV感染率与胸腺瘤类型之间存在显著关联（p < 0.05）。我们进一步分析了EBV感染与重症肌无力之间的关联。然而，尽管重症肌无力胸腺瘤中的EBV感染率较高，但差异无统计学意义（p = 0.2754）。
