PRCC-TFE3 dual-fusion FISH assay: A new method for identifying PRCC-TFE3 renal cell carcinoma in paraffin-embedded tissue.

Lei Xiong,Xiancheng Chen,Baolei Miao,Weidong Gan,Hongqian Guo,Zhen Wang,Ning Liu,Dongmei Li,Donald P Bottaro

doi:10.1371/journal.pone.0185337

Lei Xiong, Xiancheng Chen + Show 7 more

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https://doi.org/10.1371/journal.pone.0185337

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Journal: PloS one	Publication Date: Sep 26, 2017
Citations: 11	License type: CC BY 4.0

Affiliation: Nanjing University, Nanjing Drum Tower Hospital

Abstract

PRCC-TFE3 renal cell carcinoma (RCC) is one of the most common types of Xp11.2 translocation renal cell carcinoma (tRCC), of which the diagnosis mainly relies on reverse transcription-polymerase chain reaction (RT-PCR) or chromosomal analysis in fresh frozen samples. Herein, we developed a new dual-fusion fluorescence in situ hybridization (FISH) probe to succinctly identify PRCC-TFE3 RCC in paraffin-embedded tissue. We immunohistochemically analyzed TFE3 and cathepsin K expression in 23 cases of Xp11.2 tRCC which had been confirmed by break-apart TFE3 FISH probe. Next, the dual-fusion FISH assay was performed on these selected cases. Twenty typical cases of clear renal cell carcinoma and 20 cases of papillary renal cell carcinoma were collected as control groups. Seven cases were finally confirmed as PRCC-TFE3 RCC by FISH detection, emerging dual-fusion signals, of which 2 cases were identified as PRCC-TFE3 RCC by RT-PCR previously. All remaining cases were negative for the PRCC-TFE3 rearrangement by FISH. The TFE3 immunohistochemistry was positive in 22/23 cases and the cathepsin K was positive in 16/23 cases. All 7 PRCC-TFE3 RCCs showed positive cathepsin K immunoreactivity. Our results reveal that PRCC-TFE3 dual-fusion FISH probe is an efficient and concise technique for diagnosing PRCC-TFE3 RCC in paraffin-embedded tissue.

Highlights

Xp11.2 translocation renal cell carcinoma, a rare subtype of renal cell carcinoma (RCC), result from gene fusions involving the TFE3 transcription factor gene[1], and it is included into the MiT family tRCCs in the recently published World Health Organization (WHO) classification of tumors of the urinary system[2]
The total 23 Xp11.2 tRCCs were definitely diagnosed by break-apart TFE3 fluorescence in situ hybridization (FISH) probe previously, and 6 cases of these Xp11.2 tRCCs were identified as ASPL-TFE3 RCC by dual-fusion FISH probe [30]
Argani et al found that the Xp11.2 tRCCs with the SFPQ-TFE3, NONO-TFE3, DVL2-TFE3, and ASPL-TFE3 gene fusions were almost cathepsin K negative by IHC, whereas a majority of PRCC-TFE3 RCCs and 6 Xp11.2 tRCCs with unknown fusion partner were cathepsin K positive [11].The result of our study showed that seven PRCC-TFE3 RCCs exhibited positive staining for cathepsin K but all of the ASPL-TFE3 RCCs were negative, which was consistent with the findings of Martignoni et al This diversity could be due to the functional differences between the fusion variants

Summary

Introduction

Xp11.2 translocation renal cell carcinoma (tRCC), a rare subtype of renal cell carcinoma (RCC), result from gene fusions involving the TFE3 transcription factor gene[1], and it is included into the MiT family tRCCs in the recently published World Health Organization (WHO) classification of tumors of the urinary system[2]. Xp11.2 tRCCs comprise 20% to 75% of paediatric renal neoplasms [3] and about 1.5% of adult RCC. A FISH assay for identifying PRCC-TFE3 renal cell carcinoma

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