- Human Pathology（Oktay、Cheng、Akgul 等，四中心）：350 例高级别（WHO/ISUP 3–4 级）透明细胞肾细胞癌（ccRCC），组织芯片集中做 BAP1、TFE3、GPNMB 免疫组化。
- 结果：BAP1 缺失 24.0%，TFE3 核阳性 12.3%，GPNMB 阳性 6.0%；TFE3 阳性在 BAP1 缺失组富集（22.6% 对 9.0%，共同 OR 3.80，p = 0.0001），各中心一致，多因素分析中 BAP1 缺失是唯一独立预测因素（校正 OR 3.00）。
- 实践意义：TFE3 阳性的 43 例中 40 例（93%）GPNMB 阴性。高级别 ccRCC 出现 TFE3 核阳性、尤其伴 BAP1 缺失时，应考虑天然表达而非易位；以 GPNMB 作为鉴别指标，可避免误诊为 Xp11 易位性 RCC。本站仅获摘要。
收录范围：PubMed 结构式摘要中英对照（文章另由期刊 @Human_Pathology 于 2026-10-26 在 X 推介）。ScienceDirect 全文需订阅且常被 Cloudflare 拦截，本站未获全文与图表。
摘要
目的：缺乏 TFE3 重排的经典透明细胞肾细胞癌（ccRCC）中可出现天然（内源性）TFE3 核表达。由于 BAP1 缺失与 mTORC1 激活及代谢应激相关，而后者促进 MiT/TFE 核转位，我们检验了高级别 ccRCC 中 BAP1 缺失是否与天然 TFE3 表达相关。
方法与结果：我们建立了来自四个中心、共 350 例高级别（WHO/ISUP 3–4 级）ccRCC 的回顾性多机构队列，在组织芯片上集中进行 BAP1、TFE3 与 GPNMB 免疫组化。预设主要终点为 BAP1 缺失与 TFE3 表达的相关性，采用按中心分层的 Cochran-Mantel-Haenszel 分析检验。BAP1 缺失见于 84/350（24.0%），TFE3 核阳性见于 43/350（12.3%），GPNMB 阳性见于 21/350（6.0%）。TFE3 阳性在 BAP1 缺失肿瘤中富集（22.6% 对 9.0%；共同比值比 3.80，95% CI 1.88–7.68，p = 0.0001），且各队列间一致（Breslow-Day p = 0.13）；多因素分析中 BAP1 缺失仍是 TFE3 表达的唯一独立预测因素（校正 OR 3.00，p = 0.001）。43 例 TFE3 阳性肿瘤中 40 例（93%）、19 例 BAP1 缺失/TFE3 阳性肿瘤中 18 例 GPNMB 阴性。
结论：天然 TFE3 表达在 BAP1 缺失的高级别 ccRCC 中显著且独立地富集，但不伴 GPNMB 表达，可据此与易位性 RCC 区分。认识这一模式并以 GPNMB 作为鉴别指标，可避免将常伴 BAP1 缺失的经典 ccRCC 误判为 Xp11 易位性 RCC。
- Human Pathology (Oktay, Cheng, Akgul and colleagues; four centres): 350 high-grade (WHO/ISUP 3–4) clear cell RCCs with central BAP1, TFE3 and GPNMB IHC on tissue microarrays.
- Results: BAP1 loss 24.0%, nuclear TFE3 12.3%, GPNMB 6.0%; TFE3 enriched in BAP1-deficient tumours (22.6% vs 9.0%, common OR 3.80, p = 0.0001), consistent across centres, with BAP1 loss the only independent predictor (adjusted OR 3.00).
- Practice point: 40 of 43 (93%) TFE3-positive tumours lacked GPNMB. Nuclear TFE3 in high-grade ccRCC, especially with BAP1 loss, can be native expression rather than translocation; GPNMB helps avoid misclassification as Xp11 translocation RCC. Abstract only.
Scope: the structured PubMed abstract (also highlighted by @Human_Pathology on X, 26 October 2026). ScienceDirect full text is subscription-only and usually blocked by Cloudflare for our fetcher; full text and figures were not obtained.
Abstract
Aims: Native nuclear TFE3 expression occurs in conventional clear cell renal cell carcinoma (ccRCC) lacking TFE3 rearrangement. Because BAP1 loss is associated with mTORC1 activation and metabolic stress that promote MiT/TFE nuclear translocation, we examined whether BAP1 loss is associated with native TFE3 expression in high-grade ccRCC.
Methods and results: We assembled a retrospective, multi-institutional cohort of 350 high-grade (WHO/ISUP grade 3-4) ccRCC from four centers, with central BAP1, TFE3, and GPNMB immunohistochemistry on tissue microarrays. The pre-specified primary endpoint was association of BAP1 loss with TFE3 expression and tested by center-stratified Cochran-Mantel-Haenszel analysis. BAP1 loss was identified in 84/350 (24.0%), nuclear TFE3 in 43/350 (12.3%), and GPNMB in 21/350 (6.0%). TFE3 positivity was enriched in BAP1-deficient tumors (22.6% vs 9.0%; common odds ratio 3.80, 95% CI 1.88-7.68, p = 0.0001), consistently across cohorts (Breslow-Day p = 0.13), and BAP1 loss remained the only independent predictor of TFE3 expression on multivariable analysis (adjusted OR 3.00, p = 0.001). GPNMB was absent in 40 of 43 (93%) TFE3-positive tumors and in 18 of 19 BAP1-loss/TFE3-positive tumors.
Conclusions: Native TFE3 expression is significantly and independently enriched in BAP1-deficient high-grade ccRCC but is not accompanied by GPNMB, distinguishing it from translocation RCC. Recognising this pattern, and using GPNMB as a discriminator, avoids misclassifying conventional, frequently BAP1-deficient ccRCC as Xp11 translocation RCC.