Ewing-like sarcomas with BCOR-CCNB3 fusion transcript: a clinical, radiological and pathological retrospective study from the Société Française des Cancers de L'Enfant

Pediatr Blood Cancer. 2014 Dec;61(12):2191-8. doi: 10.1002/pbc.25210. Epub 2014 Aug 31.

Abstract

Background: This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing-like sarcoma harboring BCOR-CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012.

Procedure: Eligibility criteria included assessment of a BCOR-CCNB3 transcript-positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis.

Results: Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow-up of 86 months. Five year overall survival and disease-free survival were respectively 76.5% (95% CI, 58%-95%) and 67.9% (95% CI, 48%-88%).

Conclusions: BCOR-CCNB3 transcript-positive Ewing-like sarcoma diagnosis should be discussed for a transcript-negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control.

Keywords: BCOR protein; Ewing sarcoma; adolescent; cyclin B3 protein; fusion oncogene protein; small cell sarcoma.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Child
  • Combined Modality Therapy
  • Cyclin B / genetics*
  • Female
  • Follow-Up Studies
  • Frankreich
  • Gene Fusion*
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary*
  • Male
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Radiography
  • Repressor Proteins / genetics*
  • Retrospective Studies
  • Sarcoma, Ewing / diagnostic imaging
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / secondary*
  • Survival Rate
  • Young Adult

Substances

  • BCOR protein, human
  • CCNB3 protein, human
  • Cyclin B
  • Proto-Oncogene Proteins
  • Repressor Proteins