Abstract
Background
Epithelioid sarcoma (ES) is a rare soft tissue neoplasm that usually arises in the
distal extremities of young adults, presents a high rate of recurrences and metastases
and frequently poses diagnostic dilemmas. In order to identify markers useful for
patient stratification purposes, we investigated the prognostic impact of clinical
and molecular patient characteristics, including the status of SMARCB1 tumour suppressor gene, in a consecutive series of ES cases.
Methods
Kaplan–Meier survival curves were compared by the log-rank test. Immunophenotyping
and SMARCB1 protein expression were analysed by immunohistochemistry or western blotting
in 40 ES patients for which tumour material was available. Cases lacking SMARCB1 protein
expression were investigated for the presence of gene mutations and gene deletions
by exon sequencing, fluorescent in situ hybridization and quantitative PCR.
Results
FNCLCC tumour grade 3 and proximal-type histology significantly correlated with shorter
overall survival (log-rank p = 0.0046 and p = 0.0001, respectively). We identified loss of SMARCB1 protein expression in the majority
of ES cases (25/40, 62.5%), including 24/34 (71%) adult cases but only 1/6 (17%) paediatric/adolescent
cases (p = 0.02, two-tailed Fisher’s exact test). The absence of protein is strongly correlated
with SMARCB1 gene deletion (p = 0.003, two-tailed Fisher’s exact test). We observed a trend towards the correlation
between SMARCB1 inactivation and both higher tumour grading and a clinical course of the disease
characterised by the occurrence of multiple relapses/metastasis.
Conclusion
These data show that both tumour grading and subtype are prognostic factors in ES.
Loss of SMARCB1 protein expression in ES is a frequent occurrence mediated by gene
deletion events, thus pointing to a crucial role of SMARCB1 in ES genesis. Analysis of SMARCB1 status in ES warrants prospective investigation as a prognostic marker and therapeutic
target.
Keywords
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Article info
Publication history
Published online: October 08, 2010
Accepted:
September 2,
2010
Received in revised form:
August 19,
2010
Received:
May 25,
2010
Identification
Copyright
© 2010 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
