Department of Pathology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
J Gastric Cancer. 2024 Oct;24(4):391-405. doi: 10.5230/jgc.2024.24.e32.
Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies.
Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity.
Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein-Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability-high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1.
These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.
Trop 家族蛋白，包括上皮细胞黏附分子（EpCAM）和 Trop-2，作为多种恶性肿瘤的潜在治疗和诊断靶点引起了关注。本研究旨在阐明这些蛋白在胃癌（GC）中的临床病理意义，并强调它们作为靶向治疗患者分层生物标志物的潜力。
对 GC 和癌前病变进行 EpCAM 和 Trop-2 的免疫组织化学（IHC）分析，对抗体进行严格的正交验证以确保特异性和敏感性。
在 49.3%的 GC 病例中观察到 Trop-2 的强烈膜染色（3+），而 EpCAM 在几乎所有病例中均强烈表达（93.2%），表明其在 GC 中广泛表达。高 Trop-2 表达水平，表现为升高的 H 评分，与 Lauren 分类的肠型、胃粘蛋白型、淋巴结转移存在、人表皮生长因子受体 2 阳性和 Epstein-Barr 病毒（EBV）阳性显著相关。在单因素和多因素分析中，高 Trop-2 表达水平的患者生存结果较差。高 EpCAM 表达水平常见于分化型组织学类型、微卫星不稳定高和 EBV 阴性癌症，与 CD3 和 CD8 T 细胞的高密度和程序性死亡配体 1 的高联合阳性评分相关。
这些结果突出了 Trop-2 和 EpCAM 的差异表达及其在 GC 中的预后意义。使用经过精心验证的抗体确保了我们的 IHC 数据的可靠性，从而为未来针对 GC 中 Trop 家族成员的治疗策略提供了坚实的基础。
