Asbestos Diseases Research Institute, University of Sydney, Sydney, NSW 2139, Australia.
Anatomical Pathology Department, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia.
Int J Mol Sci. 2018 Oct 7;19(10):3056. doi: 10.3390/ijms19103056.
Malignant pleural mesothelioma (MPM) is a deadly cancer that is caused by asbestos exposure and that has limited treatment options. The current standard of MPM diagnosis requires the testing of multiple immunohistochemical (IHC) markers on formalin-fixed paraffin-embedded tissue to differentiate MPM from other lung malignancies. To date, no single biomarker exists for definitive diagnosis of MPM due to the lack of specificity and sensitivity; therefore, there is ongoing research and development in order to identify alternative biomarkers for this purpose. In this study, we utilized primary MPM cell lines and tested the expression of clinically used biomarker panels, including CK8/18, Calretinin, CK 5/6, CD141, HBME-1, WT-1, D2-40, EMA, CEA, TAG72, BG8, CD15, TTF-1, BAP1, and Ber-Ep4. The genomic alteration of and is common in MPM and has potential diagnostic value. Changes in and genomic expression were confirmed in MPM samples in the current study using Fluorescence In situ Hybridization (FISH) analysis or copy number variation (CNV) analysis with digital droplet PCR (ddPCR). To determine whether MPM tissue and cell lines were comparable in terms of molecular alterations, IHC marker expression was analyzed in both sample types. The percentage of MPM biomarker levels showed variation between original tissue and matched cells established in culture. Genomic deletions of and , however, showed consistent levels between the two. The data from this study suggest that genomic deletion analysis may provide more accurate biomarker options for MPM diagnosis.
恶性胸膜间皮瘤（MPM）是一种致命的癌症，由石棉暴露引起，且治疗选择有限。目前 MPM 的诊断标准需要对福尔马林固定石蜡包埋组织进行多种免疫组织化学（IHC）标志物检测，以将 MPM 与其他肺部恶性肿瘤区分开来。迄今为止，由于缺乏特异性和敏感性，尚无单一的生物标志物可用于 MPM 的明确诊断；因此，正在进行研究和开发，以确定用于此目的的替代生物标志物。在这项研究中，我们利用原发性 MPM 细胞系测试了临床使用的生物标志物组合的表达，包括 CK8/18、Calretinin、CK5/6、CD141、HBME-1、WT-1、D2-40、EMA、CEA、TAG72、BG8、CD15、TTF-1、BAP1 和 Ber-Ep4。 和 的基因组改变在 MPM 中很常见，具有潜在的诊断价值。本研究使用荧光原位杂交（FISH）分析或数字液滴 PCR（ddPCR）的拷贝数变异（CNV）分析确认了 MPM 样本中 和 基因组表达的变化。为了确定 MPM 组织和细胞系在分子改变方面是否具有可比性，在两种样本类型中分析了 IHC 标志物表达。原始组织和培养中建立的匹配细胞的 MPM 生物标志物水平的百分比显示出差异。然而， 和 的基因组缺失显示出两种之间的一致水平。这项研究的数据表明，基因组缺失分析可能为 MPM 诊断提供更准确的生物标志物选择。
