PIK3CA mutations in the endocrine organs

PIK3CA encodes a vital component of PI3K-AKT signalling and is commonly mutated in many cancers. Its role has been most well-studied in thyroid neoplasia, demonstrating an association with more aggressive behaviour. The literature surrounding PIK3CA mutations is less well-established in parathyroid, adrenal and pituitary neoplasia. In the parathyroid and adrenal glands it appears more commonly mutated in carcinomas rather than benign neoplasia. In the pituitary, PIK3CA mutations have been identified in neuroendocrine tumours, more commonly in those with invasive growth. A common theme is the co-mutation of PIK3CA and other oncogenes. Additionally, mutations in PIK3CA rarely affect the germline, however germline variants are increasingly being described, with the potential for cancer predisposition as a component of Cowden-like syndrome. PIK3CA-related overgrowth spectrum (PROS) is classically caused somatic mosaic alterations, with those affected displaying rare neoplasia that has not been reported to affect the endocrine organs. Importantly, PIK3CA can sensitise tumours to targeted therapies, in addition to more recently becoming the primary target of newly developed therapeutic agents.