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Even though only 10\u201315% of the tumors metastasize, all PPGLs are considered potentially malignant. Topoisomerase 2A (TOP2A) is a protein involved in cell proliferation and has been found to be over-expressed in metastatic PPGL. To provide support whether TOP2A could serve as a prognostic marker, 88 PPGLs (of which 8 metastatic\/relapsing) and 10 normal adrenal gland samples were assessed for\n                    <jats:italic>TOP2A<\/jats:italic>\n                    mRNA expression using quantitative real-time PCR (qRT-PCR) and TOP2A immunohistochemistry. Comparisons to clinical parameters connected to metastatic behavior were made, and The Cancer Genome Atlas was used for validation of the results. A significant association between high\n                    <jats:italic>TOP2A<\/jats:italic>\n                    mRNA expression in primary PPGL and subsequent metastatic events (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in\n                    <jats:italic>SDHB<\/jats:italic>\n                    . TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with\n                    <jats:italic>TOP2A<\/jats:italic>\n                    mRNA levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.023) as well as the Ki-67 labeling index (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). To conclude, TOP2A is a potential prognostic marker as it is frequently elevated in PPGL displaying subsequent metastatic disease, and future studies in larger cohorts are warranted to determine if a TOP2A index as assessed by immunohistochemistry could be a marker of poor outcome. Additionally, elevated levels of TOP2A could indicate a potential actionable event, and future studies with topoisomerase inhibitors would be of interest.\n                  <\/jats:p>","DOI":"10.1007\/s12022-022-09746-w","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T10:20:09Z","timestamp":1674123609000},"page":"129-141","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?"],"prefix":"10.1007","volume":"34","author":[{"given":"Karolina","family":"Solhusl\u00f8kk H\u00f6se","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Stenman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrika","family":"Svahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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