NKX2.2 is a useful immunohistochemical marker for Ewing sarcoma

• Published in: The American journal of surgical pathology Vol. 36; no. 7; pp. 993 - 999
• Main Authors: Yoshida, Akihiko, Sekine, Shigeki, Tsuta, Koji, Fukayama, Masashi, Furuta, Koh, Tsuda, Hitoshi
• Format: Journal Article
• Language: English
• Published: United States 01-07-2012
• Subjects: Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Bone Neoplasms - chemistry; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Diagnosis, Differential; Gene Rearrangement; Homeodomain Proteins - analysis; Humans; Immunohistochemistry; Japan; Predictive Value of Tests; RNA-Binding Protein EWS - genetics; Sarcoma, Ewing - chemistry; Sarcoma, Ewing - genetics; Sarcoma, Ewing - pathology; Sensitivity and Specificity; Transcription Factors - analysis; Japan
• ISSN: 0147-5185; 1532-0979
• DOI: 10.1097/pas.0b013e31824ee43c

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.