TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells. Even though only 10–15% 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 TOP2A 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 TOP2A mRNA expression in primary PPGL and subsequent metastatic events ( p = 0.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in SDHB . TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with TOP2A mRNA levels ( p = 0.023) as well as the Ki-67 labeling index ( p = 0.001). 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.