Pediatric Soft Tissue Tumors With BCOR ITD Express EGFR but Not OLIG2

Pediatr Dev Pathol. 2020 Nov-Dec;23(6):424-430. doi: 10.1177/1093526620945528. Epub 2020 Aug 13.

Abstract

Introduction: Somatic internal tandem duplication of 3' of BCOR (BCOR ITD) has been found in clear cell sarcomas of the kidney (CCSK), soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and a subgroup of central nervous system high-grade neuroepithelial tumors (CNS-HGNET). BCOR ITD+ tumors share morphologic features. Expression of OLIG2 and epidermal growth factor receptor (EGFR) has been reported in CNS-HGNET with BCOR ITD. Here, we characterize OLIG2 and EGFR expression in URCS/PMMTI with BCOR ITD.

Methods: Paraffin blocks of 9 polymerase chain reaction-confirmed soft tissue BCOR ITD+ tumors (URCS/PMMTI) were immunophenotyped for OLIG2 and EGFR expression and scored semiquantitatively by percentage of positive cells and intensity of staining as negative, 1+, 2+, and 3+. Fluorescence in situ hybridization (FISH) for EGFR amplification was performed (amplification EGFR/CEP7 ratio ≥2.0).

Results: All 9 tumors showed membrane/cytoplasmic expression of EGFR, strong and diffuse (3+) in 8 cases; weak (+2) in 1. FISH detected no EGFR amplification. OLIG2 was negative in all.

Conclusions: EGFR is overexpressed in pediatric URCS/PMMTI with BCOR ITD and may be related to transcriptional upregulation of EGFR by BCOR ITD. OLIG2 negative staining differentiates URCS/PMMTI from CNS-HGNET. This finding may further support the possibility that these tumors have a different stem cell of origin.

Keywords: BCOR; BCOR ITD; EGFR; OLIG2; PMMTI; URCS.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Child, Preschool
  • ErbB Receptors / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Infant
  • Infant, Newborn
  • Male
  • Oligodendrocyte Transcription Factor 2 / metabolism*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Retrospective Studies
  • Sarcoma / genetics
  • Sarcoma / metabolism*
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology
  • Tandem Repeat Sequences*
  • Up-Regulation

Substances

  • BCOR protein, human
  • Biomarkers, Tumor
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • EGFR protein, human
  • ErbB Receptors