- AJSP（Caliò、Martignoni 等，维罗纳大学）：16 例经 FISH/分子证实的 TFEB 改变型肾细胞癌（12 例重排、4 例扩增），与透明细胞、乳头状、嫌色细胞 RCC、嗜酸细胞瘤、TFE3 重排 RCC 及 FLCN/mTOR 突变肿瘤对照，比较免疫组化与 RNA-ISH。
- 免疫组化：TFEB 三种克隆敏感性不一，Bethyl 最可靠；cathepsin K（3F9）与 GPNMB 敏感但不特异，分别标记 40%、50% 的 TFE3 重排肿瘤和部分常见肾肿瘤。
- RNA-ISH：TRIM63 在全部 TFEB 病例强阳性，但 TFE3 重排也阳性；TFEB RNA-ISH 在全部 TFEB 改变型 RCC 阳性（重排者信号更强），全部对照（含 TFE3 重排）阴性。
- 实践提示：没有 FISH 条件时，TFEB RNA-ISH 是光镜下区分 TFEB 改变型与 TFE3 重排及其他肾肿瘤最准确、成本较低的方法；cathepsin K/GPNMB 阳性不能区分 TFEB 与 TFE3。本站仅获摘要。
收录范围：PubMed 摘要中英对照。原文为订阅内容，本站未获全文与图表。
摘要
TFEB 改变型肾细胞癌是少见肿瘤，常与其他肿瘤相混淆。尽管 FISH 仍是诊断金标准，但其可及性有限，因此促使人们评估基于光学显微镜的辅助标志物。本研究比较了免疫组化与 RNA 原位杂交（RNA-ISH）检测 TFEB 改变型肾细胞癌并将其与其他肾肿瘤相鉴别的效能。对 16 例经 FISH/分子检测证实的 TFEB 改变型肾细胞癌（12 例重排，4 例扩增）进行 TFEB（3 种不同克隆）、cathepsin K（克隆 3F9）和 GPNMB 免疫组化，以及 TRIM63 和 TFEB RNA-ISH 检测。以 48 例透明细胞肾细胞癌、48 例乳头状肾细胞癌、72 例嫌色细胞肾细胞癌、48 例嗜酸细胞瘤、5 例 TFE3 重排肾细胞癌和 4 例 FLCN/mTOR 突变肾细胞肿瘤作为对照，评估并比较各方法的染色模式与诊断效能。TFEB 免疫组化敏感性不一，其中 Bethyl 检测最为可靠。Cathepsin K（克隆 3F9）和 GPNMB 敏感性高但缺乏特异性，分别标记 40% 和 50% 的 TFE3 重排肿瘤，并标记部分常见肾肿瘤。同样，TRIM63 RNA-ISH 在所有 TFEB 改变型肾细胞癌中呈强阳性，但在 TFE3 重排肿瘤中也呈阳性。相反，TFEB RNA-ISH 在所有 TFEB 改变型肾细胞癌中均有表达且具有排他性，重排肿瘤信号更强；而在包括 TFE3 重排肿瘤在内的所有对照病例中均为阴性。TFEB RNA-ISH 是检测 TFEB 改变型肾细胞癌最准确的光镜方法，能可靠地将其与 TFE3 重排肿瘤及其他肾肿瘤区分开，有望成为 FISH 的实用且具成本效益的替代方法，在缺乏分子诊断条件时尤其如此。
- AJSP (Caliò, Martignoni and colleagues, University of Verona): 16 FISH/molecularly confirmed TFEB-altered RCCs (12 rearranged, 4 amplified) were compared by IHC and RNA-ISH with clear cell, papillary and chromophobe RCC, oncocytoma, TFE3-rearranged RCC and FLCN/mTOR-mutated tumours.
- IHC: TFEB sensitivity varied across 3 clones, with the Bethyl assay most reliable; cathepsin K (3F9) and GPNMB were sensitive but not specific, labelling 40% and 50% of TFE3-rearranged tumours and subsets of common renal tumours.
- RNA-ISH: TRIM63 was strongly positive in all TFEB cases but also in TFE3-rearranged tumours; TFEB RNA-ISH was positive in all TFEB-altered RCCs (stronger in rearranged) and negative in every control, including TFE3-rearranged tumours.
- Practice point: without FISH, TFEB RNA-ISH is the most accurate and cost-effective light-microscopy method; cathepsin K/GPNMB positivity does not separate TFEB from TFE3. Abstract only.
Scope: the PubMed abstract. The article is subscription-only, so the full text and figures were not obtained.
Abstract
TFEB-altered renal cell carcinomas are rare neoplasms, frequently mimicking other tumors. Although FISH remains the diagnostic gold standard, its limited availability has prompted the evaluation of light microscopy-based ancillary markers. This study compares the performance of immunohistochemistry and RNA-ISH in detecting TFEB-altered renal cell carcinomas and distinguishing them from other renal neoplasms. Sixteen FISH/molecularly confirmed TFEB-altered renal cell carcinomas (12 rearranged, 4 amplified) were analyzed by immunohistochemistry for TFEB (3 different clones), cathepsin K (clone 3F9), and GPNMB, and RNA-ISH for TRIM63 and TFEB. Forty-eight clear cell renal cell carcinomas, 48 papillary renal cell carcinomas, 72 chromophobe renal cell carcinomas, 48 oncocytomas, 5 TFE3-rearranged renal cell carcinomas, and 4 FLCN/mTOR-mutated renal cell neoplasms served as controls. Staining patterns and diagnostic performance were assessed and compared. TFEB immunohistochemistry demonstrated variable sensitivity, with the Bethyl assay showing the greatest reliability. Cathepsin K (clone 3F9) and GPNMB displayed high sensitivity but lacked specificity, labeling 40% and 50% of TFE3-rearranged tumors, respectively, and subsets of common renal neoplasms. Similarly, TRIM63 RNA-ISH was strongly positive in all TFEB-altered renal cell carcinomas but also in TFE3-rearranged neoplasms. Instead, TFEB RNA-ISH demonstrated exclusive expression in all TFEB-altered renal cell carcinomas, with stronger signals in rearranged tumors, whereas it was negative in all control cases, including TFE3-rearranged neoplasms. TFEB RNA-ISH emerged as the most accurate light microscopy-based method for detecting TFEB-altered renal cell carcinomas, reliably distinguishing them from TFE3-rearranged and other renal tumors, potentially representing a practical and cost-effective alternative to FISH, particularly when molecular diagnostics are lacking.