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While histology and immunohistochemistry can be suggestive, diagnosis often requires exclusion of other entities followed by confirmatory molecular analysis for its characteristic <jats:italic>ASPSCR1-TFE3<\/jats:italic> fusion. Current stain-based biomarkers (such as immunohistochemistry for cathepsin K and TFE3) show relatively high sensitivity but may lack specificity, often showing staining in multiple other entities under diagnostic consideration. Given the discovery of RNA in situ hybridization (RNA-ISH) for <jats:italic>TRIM63<\/jats:italic> as a sensitive and specific marker of MiTF-family aberration renal cell carcinomas, we sought to evaluate its utility in the workup of ASPS. <jats:italic>TRIM63<\/jats:italic> RNA-ISH demonstrated high levels (H-score greater than 200) of expression in 19\/20 (95%) cases of ASPS (average H-score 330) and was weak or negative in cases of paraganglioma, clear cell sarcoma, rhabdomyosarcoma, malignant epithelioid hemangioendothelioma, as well as hepatocellular and adrenal cortical carcinomas. Staining was also identified in tumors with known subsets characterized by <jats:italic>TFE3<\/jats:italic> alterations such as perivascular epithelioid cell neoplasm (PEComa, average H-score 228), while tumors known to exhibit overexpression of TFE3 protein without cytogenetic alterations, such as melanoma and granular cell tumor, generally showed less <jats:italic>TRIM63<\/jats:italic> ISH staining (average H-scores 147 and 96, respectively). Quantitative assessment of <jats:italic>TRIM63<\/jats:italic> staining by RNA-ISH is potentially a helpful biomarker for tumors with molecular TFE3 alterations such as ASPS.<\/jats:p>","DOI":"10.1007\/s12032-024-02305-9","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T05:03:07Z","timestamp":1708664587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of TRIM63 RNA in situ hybridization (RNA-ISH) as a potential biomarker for alveolar soft-part sarcoma (ASPS)"],"prefix":"10.1007","volume":"41","author":[{"given":"Alexander S.","family":"Taylor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Mannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liron","family":"Pantanowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arul M.","family":"Chinnaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravana M.","family":"Dhanasekaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hrycaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May P.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-8884","authenticated-orcid":false,"given":"Rohit","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"2305_CR1","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.5858\/arpa.2014-0385-RS","volume":"139","author":"OI Jaber","year":"2015","unstructured":"Jaber OI, Kirby PA. 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