Novel EWSR1-POU5F1 Fusion in Soft Tissue Myoepithelial Tumors. A Molecular Analysis of 29 Cases, Including Soft Tissue, Bone and Visceral Locations Showing Common Involvement of EWSR1 Gene Rearrangement
CR Antonescu, L Zhang, NE Chang, BR Pawel, W Travis, AE Rosenberg, GP Nielsen, P Dal Cin, CD Fletcher. Memorial Sloan-Kettering Cancer Center, New York, NY; The Children's Hospital of Philadelphia, Philadelphia, PA; Massachusettes General Hospital, Boston, MA; Brigham&Women's Hospital, Boston, MA
Background: The diagnosis of myoepithelial tumors (MET) outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. Few reports have indicated an EWSR1 gene rearrangement in soft tissue MET, and, in one case each, the fusion partner was identified as being either PBX1 or ZNF444. However, larger studies to investigate if these genetic abnormalities are recurrent or if restricted to the soft tissue location are lacking.
Design: 29 MET from mainly soft tissue, but also bone & visceral locations, showing classic morphologic features and supporting immunoprofile, with available tissue were included for molecular analysis. Patient age ranged from 1-70 years old. Gene rearrangements in EWSR1, PBX1 and ZNF444 were investigated by FISH. In 2 cases with EWSR1 rearrangement and frozen tissue available, 3'RACE was performed to identify potential novel fusion partners.
Results: EWSR1 gene rearrangement by FISH was detected in 59% cases. A novel EWSR1-POU5F1 was identified in a pediatric soft tissue MET by 3'RACE and subsequently confirmed in 2 additional soft tissue tumors in young adults, but not in other locations. The presence of a EWSR1-PBX1 was seen in one soft tissue tumor, while EWSR1-ZNF444 was noted in one pulmonary MET.
Conclusions: EWSR1 gene rearrangement is a common event in MET irrespective of their anatomic location. Many of the EWSR1 negative tumors were superficial lesions, suggesting the possibility of genetically distinct groups. A subset of soft tissue MET harbor a novel EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 1:00 PM
Platform Session: Section E, Tuesday Afternoon