Abstract
Determining the mammary origin of a metastatic or poorly differentiated carcinoma is a frequent challenge in surgical pathology. Conventional breast markers (GATA3, GCDFP-15 and mammaglobin) lose sensitivity in triple-negative and metaplastic breast carcinoma. TRPS1 (trichorhinophalangeal syndrome type 1), an atypical GATA-family transcription factor, was proposed in 2020–2021 as an immunohistochemical marker of breast lineage. This narrative review summarizes the literature up to October 2026 on TRPS1 biology, its diagnostic performance across breast carcinoma subtypes, its expression in non-mammary neoplasms and its place in current diagnostic panels. TRPS1 shows nuclear positivity in 86–99% of breast carcinomas, including triple-negative and metaplastic tumors, in which it outperforms GATA3. It is almost always negative in urothelial carcinoma, a GATA3-positive mimic of breast carcinoma. However, large studies have demonstrated expression in squamous cell carcinomas, salivary gland tumors, gynecologic carcinomas, cutaneous adnexal neoplasms and sarcomas, with overall specificities of 58–74% in recent series. Apocrine, triple-negative neuroendocrine and acinic cell carcinomas are usually negative. TRPS1 is the most sensitive breast-lineage marker currently available, particularly in triple-negative breast cancer, but it is not specific. It should be interpreted together with morphology, clinical history and a panel that includes GATA3 and markers relevant to the differential diagnosis.