Tsai Chun-Yi, Tai Tzong-Shyuan, Huang Shih-Chiang, Chen Tsung-Hsing, Hsu Jun-Te, Yeh Chun-Nan, Lai Ying-Chieh, Lin Gigin, Yeh Ta-Sen
Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Department of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 333, Taiwan.
Oncologist. 2024 Nov 18. doi: 10.1093/oncolo/oyae288.
Microsatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation.
We conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors.
Multivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts.
Frequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options.
与微卫星稳定（MSS）的胃癌相比，微卫星不稳定（MSI）的胃癌表现出淋巴结（LN）转移减少和生存率提高。然而，根据我们长期的观察，MSI病例的临床N分期（cN）经常被高估。这种差异的临床意义和潜在机制值得进一步研究。
我们对141例MSI和1119例MSS胃癌患者的临床病理数据进行了全面回顾。使用qPCR和免疫组织化学评估血管内皮生长因子-C（VEGF-C）及其受体VEGFR-3的表达。采用高参数流式细胞术分析肿瘤内CD8+T细胞亚群。
多变量分析显示，MSI状态是一个独立的预后因素，与LN比率和AJCC8病理分期一起。与MSS胃癌相比，MSI胃癌的LN比率降低，尤其是在晚期T分期时，同时保持相同的LN产量。MSI胃癌术前通过计算机断层扫描对cN的高估很常见，但在MSS胃癌中更常见被低估。MSI肿瘤中VEGF-C和VEGFR-3表达较低。与MSS胃癌相比，MSI胃癌显示CD8+T细胞总数增加，尽管表达CD45RA的效应记忆细胞（EMRA）和CD8+CXCR4+T细胞的比例较低。
MSI胃癌临床N分期的频繁高估与VEGF-C信号传导和CD8+T细胞动态有关，应谨慎解读，因为它可能会误导治疗选择。
