Utilization of a TFE3 Break-apart FISH Assay in a Renal Tumor Consultation Service
Utilization of a TFE3 Break-apart FISH Assay in a Renal Tumor Consultation Service
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DOI：
10.1097/pas.0b013e31828a69ae
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发表时间：
2013-08-01
影响因子：
5.6
通讯作者：
Argani, Pedram
中科院分区：
文献类型：
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作者：
Green, Whitney M.;Yonescu, Raluca;Argani, Pedram
Xp 11易位肾细胞癌（RCC）的特征是涉及Xp11.2断点的染色体易位，导致涉及TFE 3转录因子的基因融合。在档案材料中，诊断通常可以通过TFE 3免疫组织化学（IHC）确认，但可变固定（特别是在咨询材料中普遍存在）可能导致模棱两可的结果。已经开发了TFE 3分离荧光原位杂交（FISH）检测法来检测TFE 3基因重排;然而，尚未研究该检测法在肾肿瘤咨询实践中的实用性。我们回顾了95个连续的肾脏肿瘤咨询病例提交的规则或排除Xp 11易位RCC。FISH检测31例TFE 3重排阳性。患者年龄范围为6 - 67岁（平均值= 30岁;中位数= 28岁）。这些病例的新的或独特的形态学特征包括类似多房囊性RCC的广泛囊性改变（3例），肉瘤样转化（3例），类似嗜酸细胞瘤的嗜酸细胞区（1例），类似类癌的小梁结构（1例），类似尿路上皮原位癌的肾盂尿路上皮定植（1例），局灶性结蛋白和弥漫性消旋酶免疫反应各1例。在31例TFE 3 FISH阳性RCC中，26例通过IHC明确为TFE 3阳性，但4例为不确定，1例为阴性。在TFE 3 FISH阴性的64例病例中，50例TFE 3 IHC阴性，14例不确定。64例TFE 3 FISH阴性的肾细胞癌中有32例可分为其他公认的肾细胞癌亚型：透明细胞肾细胞癌23例，乳头状肾细胞癌5例，透明细胞乳头状肾细胞癌3例，嫌色细胞肾细胞癌1例。其他32例病例仍未分类，其中包括3例组织蛋白酶K阳性RCC，与Xp 11易位RCC非常相似。总之，TFE 3 FISH在肾肿瘤咨询材料中非常有用，通常可以解决TFE 3 IHC结果不明确的病例。鉴于优化TFE 3 IHC的困难，TFE 3 FISH对于大多数实验室来说是建立Xp 11易位RCC诊断的最佳试验。
Xp11 translocation renal cell carcinomas (RCCs) are characterized by chromosome translocations involving the Xp11.2 breakpoint, resulting in gene fusions involving the TFE3 transcription factor. In archival material, the diagnosis can often be confirmed by TFE3 immunohistochemistry (IHC), but variable fixation (especially prevalent in consultation material) can lead to equivocal results. A TFE3 break-apart fluorescence in situ hybridization (FISH) assay has been developed to detect TFE3 gene rearrangements; however, the utility of this assay in a renal tumor consultation practice has not been examined. We reviewed 95 consecutive renal tumor consultation cases submitted to rule in or rule out Xp11 translocation RCC. Thirty-one cases were positive for TFE3 rearrangements by FISH. Patients ranged from 6 to 67 years of age (mean = 30 y; median = 28 y). Novel or distinctive morphologic features of these cases included extensive cystic change simulating multilocular cystic RCC (3 cases), sarcomatoid transformation (3 cases), oncocytic areas mimicking oncocytoma (1 case), trabecular architecture mimicking a carcinoid tumor (1 case), colonization of renal pelvic urothelium mimicking urothelial carcinoma in situ (1), and focal desmin and diffuse racemase immunoreactivity (1 case each). Twenty-six of the 31 TFE3 FISH-positive RCCs were unequivocally positive for TFE3 by IHC, but 4 were equivocal, and 1 was negative. Of the 64 cases that were negative by TFE3 FISH, 50 were negative by TFE3 IHC, and 14 were equivocal. Thirty-two of the 64 TFE3 FISH-negative cases could be classified into other accepted RCC subtypes: 23 as clear cell RCC, 5 as papillary RCC, 3 as clear cell papillary RCC, and 1 as chromophobe RCC. The other 32 cases remained unclassified, including 3 cathepsin K-positive RCC that closely resembled Xp11 translocation RCC. In conclusion, TFE3 FISH is highly useful in renal tumor consultation material, often resolving cases with equivocal TFE3 IHC results. Given the difficulty of optimizing TFE3 IHC, TFE3 FISH is for most laboratories the optimal test for establishing the diagnosis of Xp11 translocation RCC.