PRCC-TFE3 Renal Cell Carcinoma:Diagnostic Study With FISH Assay And The Summary Of Clinicopathological Features

PRCC-TFE3 renal cell carcinoma(RCC),one of the most common types of Xp11.2 translocation renal cell carcinoma(tRCC),is the first documented case of Xp11.2 tRCCs.Breakpoint of the translocation in PRCC-TFE3 RCC was cloned in 1996;it was found that this translocation resulted in a fusion of the TFE3 gene on the Xp11.2 to a novel PRCC gene on 1q21.2.Previous studies showed that PRCC-TFE3 RCC presented at lower stage and less metastasis than ASPL-TFE3 RCC,however metastatic and recurrent diseases were also found to occur in some PRCC-TFE3 RCCs.Therefore,accurate,concise and early diagnosis of PRCC-TFE3 RCC is necessary to the clinic management and research.The pathological features of this tumor is slightly different from ASPL-TFE3 RCC;however PRCC-TFE3 RCC cannot be distinguished from other Xp11.2 tRCCs only depending upon pathologic morphology and immunohistochemistry(IHC).Up to now,the diagnosis of this tumor mainly relies on reverse transcription-polymerase chain reaction(RT-PCR)or chromosomal analysis in fresh frozen sample,which is difficult in FFPE archival tissue in clinical practice.Furthermore,clinicopathologic data of PRCC-TFE3 RCC and other subtypes of Xp11.2 tRCC are limited.Objectives:To accurately and succinctly identify PRCC-TFE3 RCC and summarize the clinicopathologic features,we developed a new dual-fusion fluorescence in situ hybridization(FISH)probe used on paraffin-embedded tissue and collected the clinical,pathological,and IHC features of the cases.Methods:(1)We designed the PRCC-TFE3 dual-fusion FISH probe based on the genetic characteristics.And then,this FISH assay was performed on 23 cases of Xp11.2 tRCC which had been confirmed by break-apart TFE3 FISH probe.RT-PCR was implemented on 6 cases to verify the accuracy of this FISH probe.(2)We immunohistochemically analyzed TFE3 and Cath-K expression in these cases,observed the histopathologic features and collected the clinical data of these cases.Results:(1)Seven cases were finally confirmed as PRCC-TFE3 RCC by FISH detection,emerging dual-fusion signals;(2)RT-PCR identified 2 cases of PRCC-TFE3 RCC,which was concordant with the results of FISH assay;(3)One PRCC-TFE3 RCC case was diagnosed with lung metastasis and 2 cases developed local recurrence;(4)The architecture of PRCC-TFE3 RCC was predominantly nested and focal papillary or acinar,including little clear or eosinophilic cytoplasm,and psammoma bodies could be found in 2 PRCC-TFE3 RCC cases;(5)The TFE3 IHC was positive in 22/23 Xp11.2 tRCC cases and the Cath-K was positive in 16/23 Xpl 1.2 tRCC cases.All 7 PRCC-TFE3 RCCs showed positive cathepsin K and TFE3 IHC.Conclusions:(1)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;(2)The atypical histopathologic features and TFE3 IHC cannot diagnose PRCC-TFE3 RCC;(3)The Cath-K expression in PRCC-TFE3 RCC is different from other subtypes;(4)Because of the high frequency of metastasis and recurrence in PRCC-TFE3 RCCs,differentiating the PRCC-TFE3 RCC from other types is necessary for patient management.