Implementing an integrated molecular classification for gastric cancer from endoscopic biopsies using on-slide tests.

IF 1.2 4区 医学 Q4 DEVELOPMENTAL BIOLOGY
Simona Costache, Adelina Baltan, Sofia Diaz McLynn, Mattia Pegoraro, Rebecca de Havilland, Matthew Porter, Ana Lerga, Teresa Thomas, Alina Elena Chefani, Sarah Wedden, Kim Billingham, Corrado D'Arrigo
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引用次数: 0

Abstract

The availability of more effective biological therapy can improve outcomes of gastric cancer (GC), but most patients do not have access to personalized treatment. GC molecular classification helps identify patients suitable for specific therapies and provides useful prognostic information. To date, only a small number of patients have access to molecular classification. We proposed a working molecular classification that can be delivered using on-slide tests available in most histopathology laboratories. We used eight on-slide tests [in situ hybridization (ISH) for Epstein-Barr virus-encoded small ribonucleic acid (EBER) and immunohistochemistry (IHC) for MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), E-cadherin, β-catenin and p53] to classify GC into one of six categories: GC associated with Epstein-Barr virus (GC-EBV), GC mismatch repair deficient (GC-dMMR), GC with epithelial-mesenchymal transition (GC-EMT), GC with chromosomal instability (GC-CIN), GC genomically stable (GC-GS) and GC not otherwise specified (GC-NOS)∕indeterminate. The classification has provision also for current and future on-slide companion diagnostic (CDx) tests necessary to select specific biological therapies and, as proof of principle, in this study we used three CDx tests currently required for the management of GC [human epidermal growth factor receptor 2 (Her2), programmed cell death-ligand 1 (PD-L1) 22C3 and Claudin18.2 (CLDN18.2)]. This paper describes the necessary tissue pathways and laboratory workflow and assesses the feasibility of using this classification prospectively on small endoscopic biopsies of gastric and gastroesophageal junction adenocarcinoma. This work demonstrates that such molecular classification can be implemented in the context of a histopathology diagnostic routine with little impact on turnaround times and laboratory capacity. The widespread adoption of a molecular classification for GC will help refine prognosis and guide the choice of more appropriate biological therapy for these patients.

利用滑动测试对内镜活检的胃癌进行综合分子分类。
更有效的生物疗法可改善胃癌(GC)的治疗效果,但大多数患者无法获得个性化治疗。胃癌分子分类有助于确定适合特定疗法的患者,并提供有用的预后信息。迄今为止,只有少数患者可以获得分子分类。我们提出了一种有效的分子分类方法,可通过大多数组织病理学实验室都有的滑动检测提供。我们使用八种滑动测试(原位杂交(ISH)检测 Epstein-Barr 病毒编码的小核糖核酸(EBER),免疫组化(IHC)检测 MutL 同源体 1 (MLH1)、PMS1 同源体 2 (PMS2)、MutS 同源体 2 (MSH2)、MutS 同源体 6 (MSH6)、E-cadherin、β-catenin 和 p53)将 GC 分为六类:与 Epstein-Barr 病毒相关的 GC(GC-EBV)、错配修复缺陷的 GC(GC-dMMR)、上皮-间质转化的 GC(GC-EMT)、染色体不稳定的 GC(GC-CIN)、基因组稳定的 GC(GC-GS)和未指定的 GC(GC-NOS)∕不确定。该分类还为目前和未来选择特定生物疗法所需的滑动辅助诊断(CDx)检验提供了规定,作为原理验证,我们在本研究中使用了目前治疗 GC 所需的三种 CDx 检验[人表皮生长因子受体 2(Her2)、程序性细胞死亡配体 1(PD-L1)22C3 和 Claudin18.2 (CLDN18.2)]。本文介绍了必要的组织途径和实验室工作流程,并评估了在胃癌和胃食管交界处腺癌的小型内窥镜活检中前瞻性使用这种分类方法的可行性。这项工作表明,这种分子分类可以在组织病理学诊断常规中实施,对周转时间和实验室能力的影响很小。胃癌分子分类的广泛采用将有助于完善预后,并指导这些患者选择更合适的生物疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
1.70
自引率
20.00%
发文量
221
审稿时长
3-8 weeks
期刊介绍: Romanian Journal of Morphology and Embryology (Rom J Morphol Embryol) publishes studies on all aspects of normal morphology and human comparative and experimental pathology. The Journal accepts only researches that utilize modern investigation methods (studies of anatomy, pathology, cytopathology, immunohistochemistry, histochemistry, immunology, morphometry, molecular and cellular biology, electronic microscopy, etc.).
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