title: Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors.
abstract: We report the development of a reverse transcriptase polymerase chain reaction assay that reliably detects the ETV6-NTRK3 chimeric RNA characteristic of infantile fibrosarcoma and the cellular variant of congenital mesoblastic nephroma (CMN) in formalin-fixed, paraffin-embedded tissue blocks. The 188 base pair polymerase chain reaction fusion product was detected in 11 of 12 cases of cellular CMN from which a larger sized control RNA band could be amplified, and even in 7 of 8 cases in which the control band was not detectable. A variety of other tumors that are in the histologic differential diagnosis of cellular CMN yielded negative results, including four classic CMNs, four rhabdoid tumors of the kidney, and four clear cell sarcomas of the kidney, confirming the assay's specificity. We further demonstrate the assay's utility by illustrating two cases of molecularly confirmed cellular CMN that mimicked rhabdoid tumor and clear cell sarcoma of the kidney. In contrast to previous reports, five mixed CMNs that had both classic and cellular areas all lacked the ETV6-NTRK3 fusion transcript. These results suggest that cases morphologically defined as mixed CMN may represent a mixed group of genetically distinct entities.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. pargani@pds.path.jhu.edu
authors.forename: P
authors.initials: P
authors.lastname: Argani
authors.forename: M
authors.initials: M
authors.lastname: Fritsch
authors.forename: S S
authors.initials: SS
authors.lastname: Kadkol
authors.forename: A
authors.initials: A
authors.lastname: Schuster
authors.forename: J B
authors.initials: JB
authors.lastname: Beckwith
authors.forename: E J
authors.initials: EJ
authors.lastname: Perlman
mesh_terms: D019677:Artificial Gene Fusion; D015139:Blotting, Southern; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D008297:Male; D018201:Nephroma, Mesoblastic / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm / Q000032:analysis*; D020812:Receptor, trkC / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012334:RNA, Neoplasm; D020812:Receptor, trkC; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein