Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
PhenoPath Laboratories, Seattle, WA 98103.
Hum Pathol. 2019 May;87:65-74. doi: 10.1016/j.humpath.2019.02.008. Epub 2019 Mar 6.
TFE3 rearrangements are characteristic of alveolar soft part sarcomas (ASPS), Xp11.2 translocation renal cell carcinomas (Xp11-RCC), and other rare tumors. Immunohistochemistry for TFE3 protein has been considered by some to be a reliable surrogate for TFE3 molecular studies, although others disagree. We compared 2 methods for TFE3 immunohistochemistry to determine if technical differences underlie these differences. Ninety-eight archival cases of mixed type, 19 ASPS, and 8 Xp11-RCC were stained for TFE3 at Laboratory A and Laboratory B using routine protocols. Positive controls were normal human testis (Laboratory A) and Xp11-RCC (Laboratory B). Nuclear staining was scored as "negative," "1+" (<10%), "2+" (10%-50%), and "3+" (>50%). Intensity was scored as "negative," "weak," "moderate," or "strong." Only moderate-strong, 2+ or 3+ staining was considered positive. Laboratory A results were as follows: archival cases (42 of 98, 43%), ASPS (16 of 19, 84%), and Xp11-RCC (7 of 8, 88%). Laboratory B results were as follows: archival cases (5 of 98, 5%), ASPS (14 of 19, 74%), and Xp11-RCC (5 of 8, 63%). TFE3 fluorescence in situ hybridization was positive in all tested ASPS and Xp11-RCC. The overall sensitivity and specificity of TFE3 immunohistochemistry for TFE3-rearranged neoplasms were 85% (23/27) and 57% (56/98) at Laboratory A and 70% (19/27) and 95% (93/98) at Laboratory B. Technical differences, in particular, the type of control tissue, likely account for these different results. The results of our study and prior studies suggest that TFE3 immunohistochemistry should play only a minor role (if any) in the diagnosis of TFE3-rearranged tumors, with fluorescence in situ hybridization representing the preferred method.
TFE3 重排是肺泡软组织肉瘤（ASPS）、Xp11.2 易位肾细胞癌（Xp11-RCC）和其他罕见肿瘤的特征。一些人认为 TFE3 蛋白免疫组化是 TFE3 分子研究的可靠替代方法，尽管其他人不同意。我们比较了 2 种 TFE3 免疫组化方法，以确定是否存在技术差异导致了这些差异。98 例混合性、19 例 ASPS 和 8 例 Xp11-RCC 存档病例在实验室 A 和实验室 B 中使用常规方案进行 TFE3 免疫组化染色。阳性对照为正常人类睾丸（实验室 A）和 Xp11-RCC（实验室 B）。核染色评分“阴性”、“1+”（<10%）、“2+”（10%-50%）和“3+”（>50%）。强度评分“阴性”、“弱”、“中”或“强”。只有中度-强、2+或 3+染色被认为是阳性。实验室 A 的结果如下：存档病例（98 例中的 42 例，43%）、ASPS（19 例中的 16 例，84%）和 Xp11-RCC（8 例中的 7 例，88%）。实验室 B 的结果如下：存档病例（98 例中的 5 例，5%）、ASPS（19 例中的 14 例，74%）和 Xp11-RCC（8 例中的 5 例，63%）。所有测试的 ASPS 和 Xp11-RCC 的 TFE3 荧光原位杂交均为阳性。TFE3 免疫组化在 TFE3 重排肿瘤中的总体敏感性和特异性分别为实验室 A 的 85%（23/27）和 57%（56/98），实验室 B 的 70%（19/27）和 95%（93/98）。技术差异，特别是对照组织的类型，可能导致了这些不同的结果。我们的研究和先前的研究结果表明，TFE3 免疫组化在 TFE3 重排肿瘤的诊断中应仅起次要作用（如果有的话），荧光原位杂交是首选方法。
