Endocrine Abstracts

Most of adrenocortical tumors (ACT) are benign and non-functioning tumors, in contrast to adrenocortical carcinomas (ACC), which are rare and usually very aggressive tumors with a poor prognosis. The pathological discrimination between adrenocortical adenomas (ACA) and ACC is mainly based on unspecific and subjective histological features, resulting in inaccurate diagnosis in several cases. Numerous studies have previously described the potential value of immunohistochemistry (IHC) markers, such as Insulin like-growth factor 2 (IGF2) and the proliferation marker, Ki-67, to detect malignancy in ACT. However, these data were not compiled before. This review aimed to collect the evidence on the potential diagnosis value of IGF2 and Ki-67 immunostaining for ACT. In addition, a meta-analysis was conducted to assess the accuracy of Ki-67 as diagnostic marker for ACC. The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The literature search was carried out in three electronic databases, including PubMed, Scopus, and Web of Science. A total of 25 studies met the pre-defined eligibility criteria being enrolled in the systematic review. Among these, 10 reports assessing Ki-67 IHC expression were identified as eligible for the meta-analysis. All the studies assessing IGF2 expression reported higher levels of this protein in ACC when compared to ACA, despite the differential immunostaining evaluation among the studies. The diagnostic performance of Ki-67 was assessed at the most widely used threshold (5% of stained cells) among the included studies. Ki-67 showed a pooled sensitivity, specificity, and log diagnosis odds ratio of 0.82 (95%CI: 0.65 to 0.92), 0.98 (95%CI: 0.95 to 0.99), and 4.26 (95%CI: 3.40 to 5.12), respectively. At the 5% cut-off value, the area under the summary receiver operating characteristic curve (sROC) was 0.949. As conclusion, Ki-67 marker for a 5% cut-off value showed an excellent specificity but only moderate sensitivity, which translates the failure to diagnosis all ACC. Hence, different Ki-67 thresholds should be considered in the future. Additionally, more studies using similar immunohistochemistry analysis methodologies are needed to assess the accuracy of IGF2 for ACT differential diagnosis.