Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
Mod Pathol. 2023 Nov;36(11):100303. doi: 10.1016/j.modpat.2023.100303. Epub 2023 Aug 12.
Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on immunohistochemistry can be used to screen for FH-deficient RCC, but their sensitivity and specificity are not perfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. We compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. We included genetically confirmed FH-deficient RCCs (n = 58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC) (n = 83), clear cell RCCs (n = 188), chromophobe RCCs (n = 128), and papillary RCCs (pRCC) (n = 97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 had 100% sensitivity and 91.4% specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5% of TFE3-tRCCs and 21.6% of pRCCs. 2SC showed 100% sensitivity and 88.9% specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCCs, and chromophobe RCCs. FH was 100% specific but 84.5% sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. Our findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious of FH-deficient RCC and should be referred for FH genetic tests.
琥珀酸脱氢酶（FH）缺陷型肾细胞癌（RCC）是一种罕见且独特的肾癌亚型，由 FH 基因突变引起。免疫组织化学中 FH 阴性和 s-2-琥珀酰半胱氨酸（2SC）阳性可用于筛选 FH 缺陷型 RCC，但它们的敏感性和特异性并不完美。醛酮还原酶 1B10（AKR1B10）在 RCC 中的表达尚不清楚，AKR1B10 是一种醛酮还原酶，可催化辅酶依赖性氧化还原反应。我们比较了 AKR1B10、2SC 和 FH 作为 FH 缺陷型 RCC 的诊断生物标志物。我们纳入了经基因证实的 FH 缺陷型 RCC（n=58）、经基因证实的 TFE3 易位 RCC（TFE3-tRCC）（n=83）、透明细胞 RCC（n=188）、嫌色细胞 RCC（n=128）和乳头状 RCC（pRCC）（n=97）。AKR1B10、2SC 和 FH 是有信息的诊断标志物。AKR1B10 对 FH 缺陷型 RCC 的敏感性为 100%，特异性为 91.4%。AKR1B10 在 26.5%的 TFE3-tRCC 和 21.6%的 pRCC 中的特异性较低。2SC 的敏感性为 100%，特异性为 88.9%。然而，2SC 的特异性在多种 RCC 中表现明显，包括 pRCC、TFE3-tRCC、透明细胞 RCC 和嫌色细胞 RCC。FH 的特异性为 100%，但敏感性为 84.5%。AKR1B10 是一种高度敏感和特异的诊断生物标志物。我们的研究结果表明，联合使用 AKR1B10 和 2SC 筛查 FH 缺陷型 RCC 具有价值。AKR1B10+/2SC+/FH-病例可诊断为 FH 缺陷型 RCC。AKR1B10+/2SC+/FH+患者高度怀疑 FH 缺陷型 RCC，应进行 FH 基因检测。
