EWS rearrangement in Ewing's sarcoma and peripheral neuroectodermal tumor. Molecular detection and correlation with cytogenetic analysis and MIC2 expression.

The translocation t(11;22)(q24;q12) can be identified in its classical or variant form in approximately 90% of cases of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET). In this tumor group in which the histopathologic diagnosis is often one of exclusion, the cytogenetic demonstration of this translocation has become an invaluable positive diagnostic marker. With the recent cloning of the breakpoint regions of the t(11;22), molecular genetic approaches to the detection of this translocation have become possible. By Southern blotting, the position of the breakpoints on chromosome 22 has been found to be tightly clustered within a 7-kilobase (kb) fragment of the genomic DNA, within a gene designated EWS. In the present study, we examined the efficacy of an EWS complementary DNA (cDNA) probe in detecting the t(11;22) in Southern blots of EcoRI- or HindIII-digested DNA extracted from cases of ES and PNET. We also compared the results of the molecular and cytogenetic analysis with the expression of the ES cell surface antigen MIC2, as demonstrated by immunoperoxidase staining with the monoclonal antibodies O13 and HBA71. Twenty-three specimens were studied, including 18 ES and five PNET. Of 16 cases with clonally abnormal karyotypes, 14 (88%) showed a typical or variant t(11;22). Rearrangements were demonstrated within the EWS gene with the EWS cDNA probe in 20 of 23 specimens (87%), including all of the 14 cases, as well as in one case that displayed clonal numerical chromosome abnormalities only. The MIC2 antigen was expressed in 19 of 20 cases (95%), including all three cases lacking EWS rearrangement.(ABSTRACT TRUNCATED AT 250 WORDS)