Yamamoto Gou, Ito Tetsuya, Suzuki Okihide, Kamae Nao, Kakuta Miho, Takahashi Akemi, Iuchi Katsuya, Arai Tomio, Ishida Hideyuki, Akagi Kiwamu
Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama 362-0806, Japan.
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama 350-8550, Japan.
Oncol Lett. 2023 Sep 29;26(5):494. doi: 10.3892/ol.2023.14081. eCollection 2023 Nov.
Microsatellite instability (MSI) testing, an established technique that has gained prominence in recent years for its predictive potential regarding the efficacy of immune checkpoint inhibitors, is used to evaluate DNA mismatch repair (MMR) deficiency (dMMR). As with other methods, the immunohistochemistry (IHC) of MMR proteins is also widely adopted. Although both techniques have been validated, their concordance rate remains unknown, particularly regarding non-colorectal cancer. Therefore, the aim of the present study was to explore and elucidate their concordance in the context of gastric cancer (GC). A total of 489 surgically resected primary GC tissues were analyzed to compare the results yielded by the MSI test and those from IHC. Of 488 GC cases, 56 (11.5%) exhibited a loss of MMR proteins, whereas 52 (10.7%) were classified as high-frequency MSI (MSI-H). The concordance rate between these two categories was 99.2%. The microsatellite markers BAT26 and MONO27 demonstrated 100% sensitivity and 99.5% specificity in detecting dMMR GC. In addition, histopathological analysis revealed that MSI-H was more prevalent in GCs exhibiting coexisting Tub2 and Por1 subtypes. However, four discordant cases were observed. All four cases were microsatellite-stable cases but exhibited loss of MLH1 protein expression with hypermethylation of the promoter. The results of the present study highlight that while there is a strong concordance between MSI and IHC testing results for determining dMMR status, IHC testing may offer superior efficacy in detecting dMMR.
微卫星不稳定性（MSI）检测是一项近年来因其对免疫检查点抑制剂疗效的预测潜力而备受瞩目的成熟技术，用于评估DNA错配修复（MMR）缺陷（dMMR）。与其他方法一样，MMR蛋白的免疫组织化学（IHC）也被广泛采用。尽管这两种技术都已得到验证，但其一致性率仍不清楚，尤其是在非结直肠癌方面。因此，本研究的目的是在胃癌（GC）背景下探索并阐明它们的一致性。共分析了489例手术切除的原发性GC组织，以比较MSI检测结果与IHC检测结果。在488例GC病例中，56例（11.5%）表现出MMR蛋白缺失，而52例（10.7%）被归类为高频MSI（MSI-H）。这两类之间的一致性率为99.2%。微卫星标记BAT26和MONO27在检测dMMR GC时显示出100%的敏感性和99.5%的特异性。此外，组织病理学分析显示，MSI-H在同时存在Tub2和Por1亚型的GC中更为普遍。然而，观察到4例不一致的病例。所有4例均为微卫星稳定病例，但表现出MLH1蛋白表达缺失且启动子甲基化。本研究结果强调，虽然MSI和IHC检测结果在确定dMMR状态方面有很强的一致性，但IHC检测在检测dMMR方面可能具有更高的效能。
