EWS-FLI1 Fusion Transcript Structure Is an Independent Determinant of Prognosis in Ewing's Sarcoma

Enrique de Alava, et al.
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Reviewers: Kenneth Blank, MD and John Han-Chih Chang, MD
Source: Journal of Clinical Oncology, Volume 16 Number 4, pg. 1248

Ewing's sarcoma is a bone tumor, which occurs in children and adolescents. It was first described in 1921 by James Ewing. Ewing's sarcoma is among a group of tumors that appear similar under the microscope, characterized by small round cells. Other such tumors include rhabdomyosarcoma, neuroblastoma, certain lymphomas and small cell lung cancer. Physicians use the clinical picture to differentiate among these tumors. For example, a small round cell tumor of the bone in a 13 year old is likely Ewing's sarcoma and not a lung cancer. However, at times the clinical picture does not allow easy differentiation and other markers must be used. One such marker is characteristic genetic changes seen in Ewing's sarcoma.

A fairly consistent finding in Ewing's tumors is a translocation of a gene from chromosome 11 (the FL11 gene) onto a gene from of chromosome 22 (the EWS gene). Using polymerase chain reaction (PCR) this genetic change is easily detected in a tumor specimen. The translocation of these two genes results in a fusion protein, which has been implicated as having a role in the initiation of cancer.

A report appearing in the April issue of the Journal of Clinical Oncology examines the prognostic significance of the EWS/FL11 translocation. Several different permutations of the translocation are known to occur with the most common type referred to as type 1. In this report 64 of the 99 evaluable patients had a type 1 translocation. The authors studied the type of translocation (type 1 vs. others), the site of the Ewing's tumor (bone vs. extra-skeletal), the bone involved (axial vs. extremity), the patients' age and the presence of metastasis as possible prognostic factors.

Using univariate and multivariate analysis, the type 1 translocation was found to be a positive prognostic factor, while the presence of metastasis was a negative factor. However, because patients in the study were treated with different forms of chemotherapy, the significance of the finding is clouded. Whether this new information will influence current treatment is unclear but in light of as similar report published in 1996, further studies of the prognostic significance of the type of translocation are warranted.