Mereiter Stefan, Polom Karol, Williams Coralie, Polonia Antonio, Guergova-Kuras Mariana, Karlsson Niclas G, Roviello Franco, Magalhães Ana, Reis Celso A
I3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-465 Porto, Portugal.
IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal.
J Clin Med. 2018 Sep 5;7(9):256. doi: 10.3390/jcm7090256.
Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant ( < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting.
微卫星不稳定性（MSI）是胃癌的一种独特分子亚型。近年来，MSI的临床后果以及针对这种特殊癌症亚型的治疗机会变得明显。然而，尽管MSI对患者分层很重要，但诊断所需的时间和资源仍然是一个障碍。为了寻找胃癌中MSI的新标志物，我们评估了13例MSI和17例微卫星稳定（MSS）病例队列中五种癌症相关聚糖表位的表达。我们的分析显示，桑福德-弗里德赖希（TF）抗原的表达与MSI状态之间存在高度显著（<0.001）的关联。因此，我们在此展示了胃癌中首个MSI单一标志物的鉴定，其特异性为94%（16/17），敏感性为69.2%（9/13），阴性预测值为80%（16/20），阳性预测值为90%（9/10）。通过基于简单抗体的检测方法检测到的TF抗原对癌症具有高度特异性，在胃健康上皮和癌前上皮中无法检测到。这一发现为新的研究奠定了基础，并有望改善临床环境中MSI的快速鉴定。
