title: YWHAE-FAM22 endometrial stromal sarcoma: diagnosis by reverse transcription-polymerase chain reaction in formalin-fixed, paraffin-embedded tumor.
abstract: A subset of endometrial stromal sarcoma harbors t(10;17)(q23;p13), which results in the genetic fusion between YWHAE and 1 of 2 highly homologous FAM22 family members-FAM22A or FAM22B. In contrast to classic low-grade endometrial stromal sarcoma with JAZF1-SUZ12 fusions, YWHAE-FAM22 endometrial stromal sarcoma displays high-grade histologic features and is associated with more aggressive disease course. Ancillary fluorescence in situ hybridization assay demonstrating the presence of YWHAE rearrangement can be used to support the diagnosis, but the detection of fusion transcript would be the most definitive test. We describe here an optimized reverse transcription-polymerase chain reaction assay for detection of YWHAE-FAM22 fusion transcript in formalin-fixed and paraffin-embedded tumor samples. We studied a series of 6 YWHAE-FAM22 endometrial stromal sarcomas, 7 JAZF-SUZ12 endometrial stromal sarcomas, 3 JAZF1-PHF1/EPC1-PHF1 endometrial stromal sarcomas, 6 undifferentiated endometrial sarcomas, 4 uterine leiomyosarcomas, and 4 uterine adenosarcomas. All 6 YWHAE-FAM22 endometrial stromal sarcomas were confirmed by fluorescence in situ hybridization assay, whereas all non-YWHAE-FAM22 tumors were confirmed to lack YWHAE rearrangement by fluorescence in situ hybridization assay. The reverse transcription-polymerase chain reaction assay optimized for formalin-fixed and paraffin-embedded samples detected YWHAE-FAM22 fusion transcripts in all 6 YWHAE-FAM22 endometrial stromal sarcomas and none of the 24 non-YWHAE-FAM22 uterine sarcomas. These findings show that this reverse transcription-polymerase chain reaction assay is sensitive and specific for detection of YWHAE-FAM22 fusion transcript and can serve as a useful adjunct diagnostic assay to confirm the diagnosis of YWHAE-FAM22 endometrial stromal sarcoma in formalin-fixed and paraffin-embedded tumor samples.
authors.affiliation: Department of Pathology and Laboratory Medicine, and Genetic Pathology Evaluation Center, Vancouver General Hospital, Vancouver, British Columbia, Canada V5Z 4E3.
authors.forename: Anna
authors.initials: A
authors.lastname: Isphording
authors.forename: Rola H
authors.initials: RH
authors.lastname: Ali
authors.forename: Julie
authors.initials: J
authors.lastname: Irving
authors.forename: Angela
authors.initials: A
authors.lastname: Goytain
authors.forename: Nataliya
authors.initials: N
authors.lastname: Nelnyk
authors.forename: Lien N
authors.initials: LN
authors.lastname: Hoang
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
mesh_terms: D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics*; D016612:Paraffin Embedding; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000473:pathology*
chemical_list: D015514:Oncogene Proteins, Fusion; C576541:YWHAE-FAM22 fusion protein, human; D005557:Formaldehyde