Zhong Minghao, Weisman Paul, Zhu Bing, Brassesco Maria, Yang Youfeng, Linehan W Marston, Merino Maria J, Zhang David, Rohan Stephen, Cai Dongming, Yang Ximing
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Diagn Mol Pathol. 2013 Jun;22(2):107-11. doi: 10.1097/PDM.0b013e318278962e.
Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) is a subtype of RCC characterized by translocations involving a breakpoint at the TFE3 gene (Xp11.2). Moderate to strong nuclear TFE3 immunoreactivity has been recognized as a specific diagnostic marker for this type of tumor. However, exclusive cytoplasmic localization of a TFE3 fusion protein was reported in UOK 145 cells, a cell line derived from an Xp11.2 RCC harboring the PSF-TFE3 translocation. If reproducible using immunohistochemistry (IHC), this finding would have important implications for pathologists in the diagnosis of Xp11.2 RCC, calling into question the specificity of nuclear immunoreactivity for TFE3 in these tumors. The purpose of this study was to determine whether the above-noted cytoplasmic localization of the TFE3 fusion protein could be reproduced using IHC. UOK 145 cells and fresh frozen tissue from 2 clinical cases of Xp11.2 RCC found to harbor the PSF-TFE3 gene rearrangement (by cytogenetic testing) were collected. All samples were subjected to histopathologic evaluation by board-certified pathologists, TFE3 IHC, reverse transcription polymerase chain reaction, and Sanger sequencing analysis. A strong nuclear TFE3 immunoreactivity was demonstrated in all samples including the UOK 145 cell line. No cytoplasmic immunoreactivity was seen. Reverse transcription polymerase chain reaction and Sanger sequencing confirmed the previously reported PSF-TFE3 gene fusion between exon 9 of PSF and exon 6 of TFE3 in the UOK 145 cell line and in one of 2 clinical cases of Xp11.2 RCC. A novel PSF-TFE3 gene fusion between exon 9 of PSF and exon 5 of TFE3 was detected in the second clinical case of Xp11.2 RCC.
Xp11.2易位性肾细胞癌（Xp11.2 RCC）是肾细胞癌的一种亚型，其特征是涉及TFE3基因（Xp11.2）断点的易位。核TFE3免疫反应性中度至强已被公认为这类肿瘤的特异性诊断标志物。然而，在UOK 145细胞中报道了TFE3融合蛋白仅定位于细胞质，UOK 145细胞系源自携带PSF-TFE3易位的Xp11.2 RCC。如果通过免疫组织化学（IHC）可重复这一发现，这一结果对于病理学家诊断Xp11.2 RCC具有重要意义，这使得人们质疑这些肿瘤中TFE3核免疫反应性的特异性。本研究的目的是确定是否可以通过IHC重现上述TFE3融合蛋白的细胞质定位情况。收集了UOK 145细胞以及2例经细胞遗传学检测发现携带PSF-TFE3基因重排的Xp11.2 RCC临床病例的新鲜冰冻组织。所有样本均由具备资质的病理学家进行组织病理学评估、TFE3 IHC、逆转录聚合酶链反应和桑格测序分析。在所有样本（包括UOK 145细胞系）中均显示出强烈的核TFE3免疫反应性。未观察到细胞质免疫反应性。逆转录聚合酶链反应和桑格测序证实了在UOK 145细胞系以及2例Xp11.2 RCC临床病例中的1例中，先前报道的PSF第9外显子与TFE3第6外显子之间存在PSF-TFE3基因融合。在Xp11.2 RCC的第二例临床病例中检测到一种新的PSF第9外显子与TFE3第5外显子之间的PSF-TFE3基因融合。
