Background and Objectives:Gastric cancer (GC) is one of the most commonly diagnosed cancers and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia and colleagues proposed an on-slide classification; however, this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein–Barr virus (GC EBV+), GC with mismatch-repair deficiency (GC dMMR), GC with epithelial–mesenchymal transformation (GC EMT), GC with chromosomal instability (GC CIN), CG that is genomically stable (GC GS) and GC not otherwise specified (GC NOS). This classification also has a provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here, we assess the implementation and feasibility of this inclusive working classification.Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms and assigned each case to a specific molecular subtype.Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC CIN cases were 23%, GC GS cases were 29%, and GC NOS cases were 8%.Conclusions: This working classification uses markers that are widely available in histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.
背景与目的：胃癌是全球最常见确诊的癌症之一，也是癌症死亡的第四大原因。个体化治疗可改善胃癌预后，而选择合适疗法需要分子分型指导。相较于全面基因组分析，采用玻片生物标志物和福尔马林固定石蜡包埋组织的分类方法更具实用性。2016年Setia团队提出的玻片分类法尚未广泛应用，本研究在此基础上改良形成包含六个亚型的分类系统：EB病毒相关型胃癌、错配修复缺陷型胃癌、上皮间质转化型胃癌、染色体不稳定型胃癌、基因组稳定型胃癌及非特指型胃癌。该分类体系同时整合了当前及新兴靶向治疗的生物标志物检测方案。本研究旨在评估这一包容性工作分类法的实施可行性与临床应用价值。 材料与方法：从福尔马林固定石蜡包埋组织库中选取79例手术切除病例构建组织微阵列库。采用限定性玻片标志物检测组合，通过既定判读算法将每个病例归入特定分子亚型。 结果：各亚型分布比例为：EB病毒相关型6%、错配修复缺陷型20%、上皮间质转化型14%、染色体不稳定型23%、基因组稳定型29%、非特指型8%。 结论：该工作分类法采用的标志物在组织病理学中易获取且便于判读，92%的病例可获得明确诊断分型，各亚型比例与已发表系列研究相符，具备大规模实施的可行性，值得开展内镜活检标本的验证研究。
Implementing an On-Slide Molecular Classification of Gastric Cancer: A Tissue Microarray Study
肿瘤(癌症)患者之家