RELA Fusion in Supratentorial Extraventricular Ependymomas: A Morphologic, Immunohistochemical, and Molecular Study of 43 Cases

Am J Surg Pathol. 2019 Dec;43(12):1674-1681. doi: 10.1097/PAS.0000000000001342.

Abstract

Supratentorial extraventricular ependymomas (STEEs) are relatively rare ependymomas, and their pathologic and genetic characteristics are still poorly understood. The aim of this study was to determine the histologic, immunohistochemical, and RELA fusion features, as well as to clarify in more detail the clinical courses of STEEs. Data from a total of 43 patients with STEEs was analyzed retrospectively. The status of RELA fusion was evaluated using fluorescence in situ hybridization. The expression levels of L1CAM, p65, cyclin D1, and p53 were assessed using immunohistochemistry. Progression-free survival and overall survival were calculated via Kaplan-Meier estimation using the log-rank test. Among all 43 STEEs, 65.1% (28/43) are positive for RELA fusion. Interestingly, almost half of the patients with RELA fusion-positive ependymomas are adults (13/28), and 89.3% (25/28) cases are anaplastic ependymomas, which suggests that RELA fusion testing is necessary in adults with STEEs. We investigated the immunohistochemical status of p65, L1CAM and CCND1 protein expression for their ability to predict RELA fusion status. RELA fusion-positive STEEs are frequently associated with expression of p65 (85.2%), L1CAM (85.2%), and CCND1 (81.5%). The accuracy of predicting RELA fusion status was much higher when the expression of p65 and L1CAM was combined, that is, when both were immunopositive. The status of RELA fusion, p53 overexpression, and extent of tumor resection are significantly associated with prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Child
  • Child, Preschool
  • Cyclin D1 / analysis
  • Disease Progression
  • Ependymoma / chemistry
  • Ependymoma / genetics*
  • Ependymoma / pathology
  • Ependymoma / surgery
  • Female
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence*
  • Infant
  • Male
  • Middle Aged
  • Neural Cell Adhesion Molecule L1 / analysis
  • Predictive Value of Tests
  • Progression-Free Survival
  • Retrospective Studies
  • Supratentorial Neoplasms / chemistry
  • Supratentorial Neoplasms / genetics*
  • Supratentorial Neoplasms / pathology
  • Supratentorial Neoplasms / surgery
  • Time Factors
  • Transcription Factor RelA / analysis
  • Transcription Factor RelA / genetics*
  • Tumor Suppressor Protein p53 / analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • L1CAM protein, human
  • Neural Cell Adhesion Molecule L1
  • RELA protein, human
  • TP53 protein, human
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • Cyclin D1