Diagnostic accuracy of TRIM63 RNA-ISH in MiTF-rearranged renal cell carcinomas: Results from a 331-tumor validation cohort

IF 2.6 2区医学 Q2 PATHOLOGY

Human pathology Pub Date : 2025-06-25 DOI:10.1016/j.humpath.2025.105862

Hyun Jung Lee , Farinaz Shokri , Maria S. Tretiakova

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引用次数: 0

Abstract

The microphthalmia-associated transcription factor rearranged renal cell carcinoma (MiTF-rRCC) comprise very heterogenous group of tumors with variable histology mimiking other renal cell tumors and often present a diagnostic challenge. Tripartite Motif Containing 63 (TRIM63) has been proposed as a novel marker of MiTF-rRCC, but its sensitivity and specificity remain unknown. The study aimed to investigate TRIM63 expression in a large independent cohort of different renal cell tumors and determine its diagnostic value in detecting MiTF-rRCC.

TRIM63 RNA in situ hybridization (RNA-ISH) was performed on 331 renal cell tumors, including 15 TFE3-translocation RCCs (TFE3-tRCC), 3 TFEB-amplified RCCs (TFEB-aRCC), 113 clear cell RCCs, 66 papillary RCCs, 27 oncocytomas, 23 chromophobe RCCs, 13 eosinophilic solid and cystic (ESC)-RCCs, 10 collecting duct carcinomas, 6 tubulocystic RCC, 4 fumarate hydratase (FH)-deficient RCCs, 51 other types of RCCs.

TRIM63 overexpression was identified in 80 % (12/15) of TFE3-tRCC, 33.3 % (1/3) of TFEB-aRCC, while being positive only in 4 % of other renal cell tumor types (12/313). Among non-MITF-rRCC positive cases, significant incidence of TRIM63 overexpression was detected in 66.7 % of tubulocystic RCC (4/6), 38.5 % of ESC-RCC (5/13) and 25 % of FH-deficient RCC (1/4). The overall performance of TRIM63 RNA-ISH assay for detecting MITF-rRCC tumors showed high specificity (96.2 %) and negative predictive value (98.4 %) with relatively lower sensitivity (72.2 %) and positive predictive value (52.0 %).

In conclusion, TRIM63 RNA-ISH can be a useful diagnostic marker of MiTF-rRCC. TRIM63 RNA-ISH could improve the diagnostic accuracy of recognizing MiTF-rRCC in an adequate histologic background and distinguishing them from other renal cell tumors.

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TRIM63 RNA-ISH在mitf重排肾细胞癌中的诊断准确性：来自331个肿瘤验证队列的结果

小眼相关转录因子重排肾细胞癌（MiTF-rRCC）是一种非常异质的肿瘤，具有与其他肾细胞肿瘤相似的可变组织学，通常具有诊断挑战性。Tripartite Motif Containing 63 （TRIM63）被认为是MiTF-rRCC的新标志物，但其敏感性和特异性尚不清楚。本研究旨在研究TRIM63在不同肾细胞肿瘤的大型独立队列中的表达，并确定其在检测MiTF-rRCC中的诊断价值。对331例肾细胞肿瘤进行TRIM63 RNA原位杂交（RNA- ish）检测，其中tfe3易位型RCC 15例，tfe3扩增型RCC 3例，透明细胞型RCC 113例，乳头状RCC 66例，嗜癌细胞型27例，厌色型23例，嗜酸性固体和囊性（ESC）型RCC 13例，集管癌10例，小管性RCC 6例，富马酸水合酶（FH）缺陷型4例，其他类型RCC 51例。TRIM63在80%（12/15）的TFE3-tRCC和33.3%（1/3）的TFEB-aRCC中过表达，而在其他肾细胞肿瘤类型中仅4%（12/313）呈阳性。在非mitf - rrcc阳性病例中，在66.7%的管性RCC（4/6）、38.5%的ESC-RCC（5/13）和25%的fh缺陷RCC（1/4）中检测到TRIM63过表达。TRIM63 RNA-ISH检测MITF-rRCC肿瘤的总体表现为高特异性（96.2%）和阴性预测值（98.4%），相对较低的敏感性（72.2%）和阳性预测值（52.0%）。综上所述，TRIM63 RNA-ISH可作为诊断MiTF-rRCC的有效标志物。TRIM63 RNA-ISH可以提高在充分的组织学背景下识别MiTF-rRCC的诊断准确性，并将其与其他肾细胞肿瘤区分开来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human pathology 医学-病理学

CiteScore

5.30

自引率

6.10%

发文量

206

审稿时长

21 days

期刊介绍： Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.