Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-0042, Japan.
Quantitative and Digital Pathology, School of Medicine, University of St. Andrews, St. Andrews, KY16 9TF, UK.
Virchows Arch. 2020 Sep;477(3):409-420. doi: 10.1007/s00428-020-02775-y. Epub 2020 Feb 27.
Mesothelin (MSLN) is a cell surface glycoprotein present in many cancer types. Its expression is generally associated with an unfavorable prognosis. This study examined the prognostic significance of MSLN expression in different areas of individual colorectal cancers (CRCs) using tissue microarrays (TMAs) by enrolling 314 patients with stage II (T3-T4, N0, M0) CRCs. Using formalin-fixed paraffin-embedded tissue blocks from patients, TMA blocks were constructed. Tissue core specimens were obtained from submucosal invasive front (Fr-sm), subserosal invasive front (Fr-ss), central area (Ce), and rolled edge (Ro) of each tumor. Using these four-point TMA sets, MSLN expression was immunohistochemically surveyed. The area-specific prognostic significance of MSLN expression was evaluated. A deep learning convolutional neural network algorithm was used for imaging analysis and evaluating our judgment's objectivity. MSLN staining ratio was positively correlated between the manual and machine-learning analyses (r = 0.71). The correlation coefficient between Ro and Ce, Ro and Fr-sm, and Ro and Fr-ss was r = 0.63, r = 0.54, and r = 0.61, respectively. Disease-specific survival curves for the MSLN-positive and MSLN-negative groups in Fr-sm, Fr-ss, and Ro were significantly different (five-year survival rates 88.1% and 95.5% (P = 0.024), 85.0 and 96.2% (P = 0.0087), 87.8 and 95.5% (P = 0.051), and 77.9 and 95.8% (P = 0.046) for Fr-sm, Fr-ss, Ce, and Ro, respectively). The analysis performed using area-specific four-point TMAs clearly demonstrated that MSLN expression in stage II CRC was relatively homogeneous within tumors. Additionally, high MSLN expression showed or tended to show unfavorable prognostic significance regardless of the tumor area.
间皮素（MSLN）是一种存在于多种癌症类型中的细胞表面糖蛋白。其表达通常与不良预后相关。本研究通过纳入 314 名 II 期（T3-T4、N0、M0）结直肠癌患者，使用组织微阵列（TMA）检查了 MSLN 表达在个体结直肠癌不同区域的预后意义。使用来自患者的福尔马林固定石蜡包埋组织块构建 TMA 块。从每个肿瘤的黏膜下侵袭前缘（Fr-sm）、浆膜下侵袭前缘（Fr-ss）、中央区域（Ce）和卷边（Ro）获得组织芯标本。使用这四点 TMA 集，免疫组织化学调查了 MSLN 表达。评估了 MSLN 表达的区域特异性预后意义。使用深度学习卷积神经网络算法进行成像分析和评估我们判断的客观性。MSLN 染色比例在手动和机器学习分析之间呈正相关（r=0.71）。Ro 与 Ce、Ro 与 Fr-sm 和 Ro 与 Fr-ss 之间的相关系数分别为 r=0.63、r=0.54 和 r=0.61。Fr-sm、Fr-ss 和 Ro 中 MSLN 阳性和 MSLN 阴性组的疾病特异性生存曲线有显著差异（五年生存率分别为 88.1%和 95.5%（P=0.024）、85.0%和 96.2%（P=0.0087）、87.8%和 95.5%（P=0.051）以及 77.9%和 95.8%（P=0.046））。使用区域特异性四点 TMA 进行的分析清楚地表明，II 期结直肠癌中 MSLN 表达在肿瘤内相对均匀。此外，无论肿瘤区域如何，高 MSLN 表达均显示或倾向于显示不良预后意义。
