Validation of PRKCB Immunohistochemistry as a Biomarker for the Diagnosis of Ewing Sarcoma

Fetal Pediatr Pathol. 2023 Apr;42(2):241-252. doi: 10.1080/15513815.2022.2117579. Epub 2022 Sep 5.

Abstract

Background: Ewing sarcoma (ES) can be confirmed by identifying the EWSR1-FLI1 fusion transcript. This study is to investigate whether immunostaining (IHC) of PRKCB-a protein directly regulated by EWSR1-FLI1 is a surrogate maker for diagnosing ES in routine practice. Methods: Microarray gene expression analyses were conducted. RKCB IHC was applied to 69 ES confirmed by morphology and molecular methods, and 41 non-Ewing small round cell tumors. EWSR1 rearrangement, EWSR1-FLI1 fusion or t(11;22)(q24;q12) were identified by fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, or cytogenetic analysis, respectively. Results: Gene array analyses showed significant overexpression of the PRKCB in ES. PRKCB IHC was positive in 19 cases of ES with EWSR1-FLI1 fusion, 3 cases with cytogenetic 11:22 translocation and 59 cases with EWSR1 rearrangement while negative in only one EWSR1 rearranged case. PRKCB IHC is sensitive (98%) and specific (96%) in detecting EWSR1 rearranged ES. Conclusions: PRKCB is a reliable antibody for diagnosing ES in routine practice.

Keywords: EWSR1; Ewing sarcoma; FLI1; PRKCB; biomarker; diagnosis; immunohistochemistry; molecular testing; validation.

MeSH terms

  • Biomarkers
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Oncogene Proteins, Fusion / genetics
  • Protein Kinase C beta / genetics
  • Protein Kinase C beta / metabolism
  • RNA-Binding Protein EWS / genetics
  • Sarcoma*
  • Sarcoma, Ewing* / diagnosis
  • Sarcoma, Ewing* / genetics

Substances

  • RNA-Binding Protein EWS
  • Biomarkers
  • Oncogene Proteins, Fusion
  • PRKCB protein, human
  • Protein Kinase C beta