166簇集分化（CD166），一种癌干细胞（CSC）标志物，和人表皮生长因子受体2（HER-2）在多种恶性肿瘤中表达，并与肿瘤进展相关。尽管关于CSC标志物和HER-2在胃癌（GC）中的重要性的研究迅速发展，它们在GC中的临床病理学、预后和诊断价值仍然不尽如人意。因此，本研究旨在调查CD166和HER-2在不同组织学类型的GC中的临床、预后和诊断意义。应用生物信息学分析基于它们在原发性GC肿瘤和正常邻近样本中的组织定位来确定CD166和HER-2表达的临床重要性。使用免疫组化（IHC）评估206个GC样本的组织微阵列（TMAs），包括印戒细胞型和肠型以及28个邻近正常组织，评估CD166和HER-2蛋白的表达模式、临床意义、预后和诊断价值。结果表明，与邻近正常组织相比，CD166（膜和胞质）和HER-2的表达在肿瘤细胞中明显上调（P=0.010，P<0.001和P=0.011，分别）。发现高水平的CD166膜表达与淋巴血管侵犯有显著相关性（P=0.006）；我们还观察到高胞质表达的CD166蛋白与SRC型中更多的浸润下浆膜（P=0.040）有显著相关性。相比之下，HER-2的表达与临床病理特征之间没有相关性。CD166和HER-2作为诊断标记物具有合理的准确性和高特异性。我们的结果确认了在SRC型中，CD166膜和胞质表达的增加在临床上具有意义，并且与该疾病的进展和更有侵袭性的肿瘤行为相关。这些发现可用于帮助确定需要不同随访策略的患者亚群，并且在这些类型的GC中可能被用作预后或诊断的生物标志物，以进行前瞻性临床应用。© 2023. 作者授权独家许可给西班牙肿瘤学会（FESEO）。

Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC.Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC).The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers.Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).