Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.
Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, 80131, Naples, Italy.
Pathol Oncol Res. 2020 Jul;26(3):1417-1427. doi: 10.1007/s12253-020-00811-5. Epub 2020 May 6.
Microsatellite instability (MSI) defines one of the four molecular groups of endometrial carcinoma identified by The Cancer Genome Atlas (TCGA). Immunohistochemistry for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) has been proposed as a widely applicable technique to identify this group in the common practice. However, the diagnostic accuracy of such approach has never been calculated. We aimed to assess: 1) the diagnostic accuracy of MMR proteins immunohistochemistry as surrogate of MSI molecular testing in endometrial carcinoma; 2) whether a combination of only two MMR proteins may be used as a still cheaper test. A systematic review and meta-analysis of was performed by searching electronic databases from their inception to September 2019. All studies assessing endometrial carcinoma with both MMR proteins immunohistochemistry and MSI molecular testing were included. Diagnostic accuracy was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves. A subgroup analysis was performed for a combination of only two MMR proteins (MLH1-MSH2 vs MSH6-PMS2). Ten studies with 3097 patients were included. Out of these, 1110 were suitable for the meta-analysis. Immunohistochemistry for all the four MMR proteins showed sensitivity = 0.96, specificity = 0.95, LR + =17.7, LR- = 0.05, DOR = 429.77, and high diagnostic accuracy (AUC = 0.988). The combination of MLH1 and MSH2 showed sensitivity = 0.88, specificity = 0.96, LR + =22.36, LR- = 0.15, DOR = 200.69, and high diagnostic accuracy (AUC = 0.9838). The combination of MSH6 and PMS2 showed the same results as the complete panel of four MMR proteins. In conclusion, MMR proteins immunohistochemistry is a highly accurate surrogate of MSI molecular testing in endometrial carcinoma. A combination of MSH6 and PMS2 may allow reducing the cost without decrease in the diagnostic accuracy.
微卫星不稳定性 (MSI) 定义了癌症基因组图谱 (TCGA) 确定的子宫内膜癌的四个分子组之一。免疫组化检测错配修复 (MMR) 蛋白（MLH1、MSH2、MSH6、PMS2）已被提议作为一种广泛适用于在常规实践中识别该组的技术。然而，这种方法的诊断准确性从未被计算过。我们的目的是评估：1) MMR 蛋白免疫组化作为 MSI 分子检测的替代方法在子宫内膜癌中的诊断准确性；2) 仅使用两种 MMR 蛋白是否可以作为一种更便宜的检测方法。通过从其开始到 2019 年 9 月在电子数据库中进行系统评价和荟萃分析。所有评估子宫内膜癌的 MMR 蛋白免疫组化和 MSI 分子检测的研究均包括在内。诊断准确性作为敏感性、特异性、阳性和阴性似然比 (LR+、LR-)、诊断比值比 (DOR) 和 SROC 曲线下的面积 (AUC) 进行评估。对于仅两种 MMR 蛋白（MLH1-MSH2 与 MSH6-PMS2）的组合进行了亚组分析。共纳入了 10 项包含 3097 例患者的研究。其中，1110 例适合进行荟萃分析。所有四种 MMR 蛋白的免疫组化均显示出敏感性=0.96，特异性=0.95，LR+=17.7，LR-=0.05，DOR=429.77，以及高诊断准确性 (AUC=0.988)。MLH1 和 MSH2 的组合显示出敏感性=0.88，特异性=0.96，LR+=22.36，LR-=0.15，DOR=200.69，以及高诊断准确性 (AUC=0.9838)。MSH6 和 PMS2 的组合与四种 MMR 蛋白的完整组合具有相同的结果。总之，MMR 蛋白免疫组化是子宫内膜癌 MSI 分子检测的高度准确替代方法。MSH6 和 PMS2 的组合可能可以降低成本而不降低诊断准确性。
