Oliveira Sofia B, Machado Mariana Q, Sousa Diana, Pereira Sofia S, Pignatelli Duarte
UMIB - Unit for Multidisciplinary Research in Biomedicine; ICBAS - School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal.
ITR - Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.
Rev Endocr Metab Disord. 2025 Apr;26(2):261-278. doi: 10.1007/s11154-025-09945-w. Epub 2025 Jan 31.
Distinguishing benign from malignant adrenocortical tumors (ACT) is not always easy, particularly for tumors with unclear malignant potential based on the histopathological features comprised of the Weiss score. Previous studies reported the potential utility of immunohistochemistry (IHC) markers to recognize malignancy, in particular the Insulin-like growth factor 2 (IGF2) and the proliferation marker, Ki-67. However, this information was not compiled before. Therefore, this review aimed to collect the evidence on the potential diagnosis utility of IGF2 and Ki-67 IHC staining. Additionally, a meta-analysis was performed to assess the Ki-67 accuracy to identify adrenocortical carcinoma. The systematic review and meta-analysis were conducted according to the PRISMA guidelines. From the 26 articles included in the systematic review, 21 articles provided individual data for IGF2 (n = 2) or for Ki-67 (n = 19), while 5 studies assessed both markers. IGF2 staining was positive in most carcinomas, in contrast to adenomas. However, the different immunostaining evaluation methods adopted among the studies impeded to perform a meta-analysis to assess IGF2 diagnostic accuracy. In contrast, for the most commonly used cut-off value of 5% stained cells, Ki-67 showed pooled specificity, sensitivity and log diagnostic odds ratio of 0.98 (95% CI 0.95 to 0.99), 0.82 (95% CI 0.65 to 0.92) and 4.26 (95% CI 3.40 to 5.12), respectively. At the 5% cut-off, Ki-67 demonstrated an excellent specificity to recognize malignant ACT. However. the moderate sensitivity observed indicates the need for further studies exploring alternative threshold values. Additionally, more studies using similar approaches are needed to assess the diagnostic accuracy of IGF2.Registration code in PROSPERO: CRD42022370389.
区分肾上腺皮质肿瘤（ACT）的良恶性并不总是容易的，特别是对于那些基于Weiss评分的组织病理学特征而恶性潜能不明确的肿瘤。先前的研究报道了免疫组织化学（IHC）标志物在识别恶性肿瘤方面的潜在效用，特别是胰岛素样生长因子2（IGF2）和增殖标志物Ki-67。然而，此前这些信息并未被汇总。因此，本综述旨在收集关于IGF2和Ki-67免疫组化染色潜在诊断效用的证据。此外，还进行了一项荟萃分析以评估Ki-67在识别肾上腺皮质癌方面的准确性。系统评价和荟萃分析是根据PRISMA指南进行的。在系统评价纳入的26篇文章中，21篇文章提供了IGF2（n = 2）或Ki-67（n = 19）的个体数据，而5项研究评估了这两种标志物。与腺瘤相比，大多数癌组织中的IGF2染色呈阳性。然而，各研究采用的不同免疫染色评估方法妨碍了进行荟萃分析以评估IGF2的诊断准确性。相比之下，对于最常用的5%染色细胞临界值，Ki-67的合并特异性、敏感性和对数诊断优势比分别为0.98（95%可信区间0.95至0.99）、0.82（95%可信区间0.65至0.92）和4.26（95%可信区间3.40至5.12）。在5%的临界值时，Ki-67在识别恶性ACT方面表现出优异的特异性。然而，观察到的中等敏感性表明需要进一步研究探索替代临界值。此外，还需要更多采用类似方法的研究来评估IGF2的诊断准确性。在PROSPERO中的注册号：CRD42022370389。
