Aida Shinsuke, Aida Junko, Naoi Miho, Kato Mai, Tsuura Yukio, Natsume Ichiro, Takubo Kaiyo
Department of Pathology, Mita Hospital, International University of Health and Welfare, Tokyo, Japan.
Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Pathol Int. 2018 Sep;68(9):503-508. doi: 10.1111/pin.12710. Epub 2018 Aug 10.
We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.
我们估计了肿瘤性和非肿瘤性间皮细胞的端粒长度,并检测了它们与石棉暴露以及间皮恶性肿瘤标志物表达的相关性。对35例非肿瘤性疾病(NN)、12例恶性间皮瘤(MM)和12例肺腺癌所致癌性胸腔积液(LA)患者的胸腔积液细胞块进行了检测。35例NN患者中有15例有提示石棉暴露的胸膜斑(NNpp+),另外20例无胸膜斑(NNpp-)。采用组织定量荧光原位杂交法测量端粒长度,并以标准化端粒与着丝粒比值表示。NN患者的端粒明显长于MM(P < 0.001)和LA(P < 0.001)患者。NNpp+患者的端粒略短于NNpp-患者(P = 0.047)。MM和LA的端粒长度几乎相同。端粒较短的NN患者倾向于出现上皮膜抗原(EMA)、CD146、葡萄糖转运蛋白1(GLUT1)和胰岛素样生长因子II信使核糖核酸结合蛋白3(IMP3)的异常表达。这些结果表明,端粒缩短及随后的基因不稳定在MM的发生发展中起重要作用。测量胸腔积液中细胞的端粒长度可能有助于MM的早期检测。