- 72 例 FH 缺陷型 RCC 中 88.9% HER2（4B5）阳性，以胞质染色为主，可伴核和/或膜着色；4 例低级别病例均为胞质+核+膜阳性。
- 30 例 HER2 阳性者 FISH 均无扩增；另两种 N 端抗体可染胞质/膜但不染核，Western blot 确认识别 185 kDa HER2。
- 在 440 例对照中，常见 RCC 亚型几乎全阴；TFE3 易位 RCC 仅 2.4%、嗜酸细胞性乳头状 RCC 22.2% 阳性——特异度 99.1%。
- 灵敏度 88.9%（优于单独 FH），特异度优于 2SC/AKR1B10；作者推荐 HER2/FH 组合作为筛查面板——对泌尿生殖病理日常鉴别有直接落地价值。
收录范围：PubMed 英文摘要及中文翻译（abstract-only）。原文为订阅制（ScienceDirect，Unpaywall 显示 closed），未采集全文、图表。
摘要
延胡索酸水合酶缺陷型肾细胞癌（FH-deficient RCC）中人表皮生长因子受体 2（HER2）的表达情况尚此前尚未系统探讨。我们对 72 例 FH 缺陷型 RCC 及 440 例其他亚型 RCC 进行了 HER2（克隆 4B5）、FH、2SC 与 AKR1B10 的免疫组化染色。88.9%（64/72）的 FH 缺陷型 RCC 呈 HER2 阳性，表现为仅胞质（6.9%）、胞质+核（47.2%）、胞质+膜（2.8%）或胞质+核+膜（31.9%）四种模式。值得注意的是，全部 4 例低级别 FH 缺陷型 RCC 均呈胞质、核与膜共同阳性。对 30 例 HER2 阳性的 FH 缺陷型 RCC 行 HER2 荧光原位杂交，均未见扩增。随后用另外两种 N 端 HER2 抗体（A21248 与 HA721178）对 27 例 FH 缺陷型 RCC 染色，可见与 4B5 类似的胞质与膜阳性，但缺乏核表达；蛋白质印迹证实三种抗体均可识别 185 kDa 的 HER2 蛋白。相比之下，透明细胞 RCC、嫌色细胞 RCC、典型乳头状 RCC、极性反转乳头状肾肿瘤及 SMARCB1 缺陷型肾髓质癌中 HER2（4B5）均阴性；而 TFE3 易位相关 RCC 中 2.4%（2/83）、嗜酸细胞性乳头状 RCC 中 22.2%（2/9）呈阳性。HER2 的灵敏度为 88.9%（优于 FH，逊于 2SC 与 AKR1B10），特异度为 99.1%（优于 2SC 与 AKR1B10，逊于 FH）；HER2/FH 组合诊断效能最佳。结论：FH 缺陷型 RCC 以普遍的胞质 HER2 染色为特征，并伴有不同程度的核/膜反应性；联合 HER2/FH 可作为有效的筛查策略。
- HER2 (clone 4B5) positivity in 88.9% of 72 FH-deficient RCCs, mainly cytoplasmic ± nuclear/membranous; all 4 low-grade cases showed cytoplasmic+nuclear+membranous staining.
- No HER2 amplification by FISH in 30 positive cases; two N-terminal antibodies stained cytoplasm/membrane but not nucleus; western blot confirmed 185 kDa HER2.
- Among 440 other RCCs, common subtypes were negative; only 2.4% of TFE3-translocation and 22.2% of oncocytic papillary RCCs positive — specificity 99.1%.
- Sensitivity 88.9% (better than FH alone); HER2/FH combination gave optimal diagnostic efficacy — practical GU screening panel.
Scope: PubMed abstract only. The article is subscription-only (ScienceDirect; Unpaywall: closed), so full text, figures and tables were not collected.
Abstract
The presence of human epidermal receptor 2 (HER2) in fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) remains unexplored. We investigated immunohistochemical staining for HER2 (clone 4B5), FH, 2SC, and AKR1B10 on 72 cases of FH-deficient RCC and 440 cases of other RCC subtypes. HER2 positivity was observed in 88.9% (64/72) of FH-deficient RCCs, manifesting as cytoplasmic only (6.9%), cytoplasmic and nuclear (47.2%), cytoplasmic and membranous (2.8%), or cytoplasmic, nuclear, and membranous (31.9%) patterns. Notably, all four cases of low-grade FH-deficient RCC exhibited cytoplasmic, nuclear, and membranous positivity. HER2 fluorescence in situ hybridization test showed no amplification in any of the 30 HER2-positive FH-deficient RCCs. Next, 27 FH-deficient RCCs stained with two additional N-terminal HER2 antibodies (A21248 and HA721178) revealed cytoplasmic and membranous positivity similar to those with 4B5 but lacked nuclear expression, and western blot confirmed recognition of the 185 kDa HER2 protein by all three antibodies. In contrast, HER2 (4B5) staining was absent in clear cell RCCs, chromophobe RCCs, typical papillary RCCs, papillary renal neoplasms with reverse polarity, and SMARCB1-deficient renal medullary carcinomas, whereas positivity was observed in 2.4% (2/83) of TFE3-translocation and 22.2% (2/9) of oncocytic papillary RCCs. HER2 achieved 88.9% sensitivity (superior to FH; inferior to 2SC and AKR1B10) and 99.1% specificity (superior to 2SC and AKR1B10; inferior to FH), with the HER2/FH combination yielding optimal diagnostic efficacy. In conclusion, FH-deficient RCCs are characterized by prevalent cytoplasmic HER2 staining with variable nuclear/membranous reactivity, and the combined HER2/FH panel may serve as an effective screening strategy.