Shimakage Misuzu, Kawahara Kunimitsu, Sasagawa Toshiyuki, Inoue Hirokazu, Yutsudo Masuo, Yoshida Akira, Yanoma Syunsuke
Clinical Research Institute and Department of Pathology, Osaka National Hospital, Japan.
Hum Pathol. 2003 Nov;34(11):1170-7. doi: 10.1053/j.humpath.2003.07.001.
There have been few studies regarding cancer progression from differentiated thyroid carcinoma to the undifferentiated one. To examine the possible involvement of Epstein-Barr virus (EBV) in this progression, 10 papillary carcinomas and 11 undifferentiated carcinomas were subjected to mRNA in situ hybridization, indirect immunofluorescence staining, polymerase chain reaction (PCR), and reverse-transcriptase PCR. mRNA in situ hybridization using a BamHIW probe revealed signals in all of the examined samples, although the signal strength was weaker in the papillary carcinomas than in the undifferentiated carcinomas. EBV nuclear antigen-2 (EBNA2) in situ hybridization produced almost the same results; however, the signals were detected less frequently in the papillary carcinomas. Indirect immunofluorescence using anti-EBNA2, anti-latent membrane protein-1 (LMP1), and anti-BZLF1 antibodies also showed positive results with high frequency and with more prominent fluorescence in undifferentiated carcinomas than in papillary carcinomas. An examination of thyroid carcinoma cell lines also confirmed these findings. EBV infected all of the thyroid carcinomas irrespective of the degree of pathological differentiation. The expression of EBV, especially of EBNA2 and LMP1 (both of which are oncogene products of EBV), was stronger in the undifferentiated carcinomas than in the papillary carcinomas. These results suggest that increased expression of EBV may be involved in the progression of thyroid papillary carcinoma to undifferentiated carcinoma.
关于甲状腺分化型癌向未分化型癌进展的研究较少。为了研究爱泼斯坦-巴尔病毒(EBV)在这一进展过程中可能发挥的作用,对10例乳头状癌和11例未分化癌进行了mRNA原位杂交、间接免疫荧光染色、聚合酶链反应(PCR)及逆转录PCR检测。使用BamHIW探针进行的mRNA原位杂交在所有检测样本中均显示出信号,尽管乳头状癌中的信号强度弱于未分化癌。EBV核抗原2(EBNA2)原位杂交产生了几乎相同的结果;然而,在乳头状癌中检测到信号的频率较低。使用抗EBNA2、抗潜伏膜蛋白1(LMP1)和抗BZLF1抗体进行的间接免疫荧光检测也显示出高频率的阳性结果,且未分化癌中的荧光比乳头状癌中更明显。对甲状腺癌细胞系的检测也证实了这些发现。EBV感染了所有甲状腺癌,无论其病理分化程度如何。EBV的表达,尤其是EBNA2和LMP1(两者均为EBV的癌基因产物)的表达,在未分化癌中比在乳头状癌中更强。这些结果表明,EBV表达增加可能参与了甲状腺乳头状癌向未分化癌的进展。