title: Xp11.2 translocation renal cell carcinoma with PSF-TFE3 rearrangement.
abstract: 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.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. minghaozhong@gmail.com
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhong
authors.forename: Paul
authors.initials: P
authors.lastname: Weisman
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Maria
authors.initials: M
authors.lastname: Brassesco
authors.forename: Youfeng
authors.initials: Y
authors.lastname: Yang
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: David
authors.initials: D
authors.lastname: Zhang
authors.forename: Stephen
authors.initials: S
authors.lastname: Rohan
authors.forename: Dongming
authors.initials: D
authors.lastname: Cai
authors.forename: Ximing
authors.initials: X
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics*; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015514:Oncogene Proteins, Fusion; C069203:TFE3 protein, human