TRIM63 Overexpression in FISH-Negative MiTF Family Altered Renal Cell Carcinoma (MiTF RCC)

作者：Rahul Mannan, Ying‐Bei Chen, Xiao Ming Wang, Yuping Zhang, Noshad Hosseini, Ankur R. Sangoi, Andrés Acosta, Sean R. Williamson, Somnath Mahapatra, Anya Chinnaiyan, Jing Hu, Ulka N. Vaishampayan, Lina Shao, Bryan L. Betz, Annette S. Kim, Xuhong Cao, Fengyun Su, Rui Wang, Pedram Argani, Noah A. Brown, Satish K. Tickoo, Arul M. Chinnaiyan, Victor E. Reuter, Saravana M. Dhanasekaran, Rohit Mehra · 发表于：Modern Pathology · 年份：2025 · DOI：10.1016/j.modpat.2025.100873 · 被引用次数：9 · 研究领域：Chromatin Remodeling and Cancer、Renal cell carcinoma treatment、interferon and immune responses

TFE3 and TFEB break-apart fluorescent in situ hybridization (FISH) assays are the "gold standard" for diagnostic confirmation of microphthalmia-associated transcription factor (MiTF) family-altered renal cell carcinoma (MiTF RCC), which includes TFE3-rearranged RCC and TFEB-altered RCC. However, FISH assays, for multiple reasons, may lead to equivocal or false-negative results, especially in cryptic fusions resulting from intrachromosomal inversions involving 5' partner genes, such as non-POU domain-containing octamer-binding protein (NONO); GRIPI-associated protein 1 (GRIPAP1); RNA-binding motif protein, X chromosome (RBMX); and RNA-binding motif protein 10 (RBM10). When FISH results are negative in cases with strong morphological suspicion of the listed tumor entities, pathologists may recommend targeted RT-PCR or panel-based RNA fusion sequencing for diagnostic confirmation. Our recent RNA in situ hybridization (RNA ISH)-based study demonstrated RNA expression of the tripartite motif containing 63 (TRIM63) to be highly enriched in TFE3-rearranged RCC and TFEB-altered RCC, including 2 FISH false-negative RCC cases harboring RBM10::TFE3 fusion. Based on these observations, we hypothesized that TRIM63 positivity could aid in diagnosing cases that are negative by conventional FISH assay but remain morphologically suspicious, representing an unmet clinical need in this area. We collected 20 RCC cases with morphological suspicion (with equivocal/indeterminate immunohistochemistr...