title: NKX2.2 is a useful immunohistochemical marker for Ewing sarcoma.
abstract: Ewing sarcoma is a high-grade round cell sarcoma that affects bones and soft tissues in children and young adults. Its diagnosis can be challenging, and the differential diagnoses include a wide variety of small round cell tumors. CD99 and FLI-1 are the currently accepted immunohistochemical markers for Ewing sarcoma, but their accuracy has been controversial. NKX2.2 is a homeodomain-containing transcription factor that plays a critical role in neuroendocrine/glial differentiation. The NKX2.2 gene was recently identified as a target of EWS-FLI-1, the fusion protein specific to Ewing sarcoma, and was shown to be differentially upregulated in Ewing sarcoma on the basis of array-based gene expression analysis. However, the immunohistochemical diagnostic potential of this marker has not been tested. We immunostained representative sections of 30 genetically confirmed Ewing sarcomas and 130 non-Ewing small round cell tumors by using an antibody to NKX2.2. Nuclear staining in at least 5% of the cells was deemed positive. Twenty-eight (93%) of the 30 Ewing sarcomas were positive for NKX2.2. The staining was diffuse (>50%) in all the positive cases and was moderate or strong in intensity for most cases (25 of 28). NKX2.2 was also positive in 14 non-Ewing tumors, including all the olfactory neuroblastomas and a minor subset of small cell carcinomas, synovial sarcomas, mesenchymal chondrosarcomas, and malignant melanomas. All the other non-Ewing tumors tested were negative for this marker. NKX2.2 is a valuable marker for Ewing sarcoma, with a sensitivity of 93% and a specificity of 89%, and aids in the differential diagnosis of small round cell tumors.
authors.affiliation: Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan. akyoshid@ncc.go.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sekine
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001859:Bone Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D015321:Gene Rearrangement; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D009687:Nuclear Proteins; D011237:Predictive Value of Tests; D034802:RNA-Binding Protein EWS / Q000235:genetics; D012512:Sarcoma, Ewing / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis*; D029961:Zebrafish Proteins
chemical_list: D014408:Biomarkers, Tumor; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish