[55] Common Homozygous SMARCB1 Deletions in Both Proximal and Distal Types of Epithelioid Sarcoma (ES) – Can Be Reliably Detected by FISH in Archival Material

Francois Le Loarer, Lei Zhang, Jean-Michel Coindre, Cristina R Antonescu. Memorial Sloan-Kettering Cancer Center, New York, NY; Institute Bergonie Cancer Center, Bordeaux, France

Background: Although conventional and proximal types of ES show distinct anatomic presentation, morphologic appearance and clinical outcome, they are defined as a morphologic spectrum of a single pathologic entity due to their common epithelial phenotype and loss of INI-1/BAF47 expression. Despite the consistent loss of protein expression by immunohistochemistry, corresponding SMARCB1 gene mutations/deletions have been only sporadically identified and mainly in the proximal type of ES. Our goal was to better characterize the incidence of SMARCB1 deletions in distal/conventional-type compared to proximal-type of ES, as a proof of principle of their common pathogenesis.
Design: FISH analysis using custom BAC RP11-71G19 covering SMARCB1 on 22q11.23 and a reference BAC probe for EWSR1 on 22q12.2 was applied on a group of 28 ES (14 distal, 14 proximal) with classic morphologic appearance and loss of INI1 expression by IHC.
Results: Homozygous SMARCB1 deletions were found in 13/14 distal and 12/14 proximal-type ES. An additional case with heterozygous deletion was found in a proximal-type ES. One case each showed two copies of SMARCB1 gene, however, the lesional tissue available for analysis was quite limited. In one of the distal-type ES with homozygous SMARCB1 deletion in the tumor, a heterozygous deletion was identified in the adjacent normal tissue in keeping with a constitutional abnormality.
Conclusions: FISH analysis using archival material detected a similarly high incidence of SMARCB1 homozygous deletions in both distal and proximal type ES, in keeping with their common pathogenesis. The presence of a constitutional/germline SMARCB1 deletion in one of the patients with distal-type ES further establishes a link with the atypical teratoid/rhabdoid tumor of the brain.
Category: Bone & Soft Tissue

Monday, March 4, 2013 1:00 PM

Poster Session II # 12, Monday Afternoon


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