TRIM63 is a sensitive and specific biomarker for MiT family aberration-associated renal cell carcinoma Journal Article
| Authors: | Wang, X. M.; Zhang, Y.; Mannan, R.; Skala, S. L.; Rangaswamy, R.; Chinnaiyan, A.; Su, F.; Cao, X.; Zelenka-Wang, S.; McMurry, L.; Xiao, H.; Spratt, D. E.; Sangoi, A. R.; Shao, L.; Betz, B. L.; Brown, N.; Tickoo, S. K.; McKenney, J. K.; Argani, P.; Gupta, S.; Reuter, V. E.; Chinnaiyan, A. M.; Dhanasekaran, S. M.; Mehra, R. |
| Article Title: | TRIM63 is a sensitive and specific biomarker for MiT family aberration-associated renal cell carcinoma |
| Abstract: | Microphthalmia-associated transcription factor (MiT) family aberration-associated renal cell carcinoma (MiTF-RCC) is a subtype of renal cell carcinoma harboring recurrent chromosomal rearrangements involving TFE3 or TFEB genes. MiTF-RCC is morphologically diverse, can histologically resemble common RCC subtypes like clear cell RCC and papillary RCC, and often poses a diagnostic challenge in genitourinary clinical and pathology practice. To characterize the MiTF-RCC at the molecular level and identify biomarker signatures associated with MiTF-RCC, we analyzed RNAseq data from MiTF-RCC, other RCC subtypes and benign kidney. Upon identifying TRIM63 as a cancer-specific biomarker in MiTF-RCC, we evaluated its expression independently by RNA in situ hybridization (RNA-ISH) in whole tissue sections from 177 RCC cases. We specifically included 31 cytogenetically confirmed MiTF-RCC cases and 70 RCC cases suspicious for MiTF-RCC in terms of clinical and morphological features, to evaluate and compare TRIM63 RNA-ISH results with the results from TFE3/TFEB fluorescence in situ hybridization (FISH), which is the current clinical standard. We confirmed that TRIM63 mRNA was highly expressed in all classes of MiTF-RCC compared to other renal tumor categories, where it was mostly absent to low. While the TRIM63 RNA-ISH and TFE3/TFEB FISH results were largely concordant, importantly, TRIM63 RNA-ISH was strongly positive in TFE3 FISH false-negative cases with RBM10-TFE3 inversion. In conclusion, TRIM63 can serve as a diagnostic marker to distinguish MiTF-RCC from other renal tumor subtypes with overlapping morphology. We suggest a combination of TFE3/TFEB FISH and TRIM63 RNA-ISH assays to improve the accuracy and efficiency of MiTF-RCC diagnosis. Accurate diagnosis of MiTF-RCC and other RCC subtypes would enable effective targeted therapy and avoid poor therapeutic response due to tumor misclassification. © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Journal Title: | Modern Pathology |
| Volume: | 34 |
| Issue: | 8 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2021-08-01 |
| Start Page: | 1596 |
| End Page: | 1607 |
| Language: | English |
| DOI: | 10.1038/s41379-021-00803-z |
| PUBMED: | 33854184 |
| PROVIDER: | scopus |
| PMCID: | PMC8298271 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2021 -- Source: Scopus |
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