Validation of potential therapeutic targets in alveolar soft part sarcoma: an immunohistochemical study utilizing tissue microarray
- 1 December 2009
- journal article
- Published by Wiley in Histopathology
- Vol. 55 (6), 750-755
- https://doi.org/10.1111/j.1365-2559.2009.03436.x
Abstract
The molecular signature of alveolar soft part sarcoma (ASPS) is a specific der(17)t(X;17)(p11.2;q25) translocation, resulting in a chimeric transcription factor (ASPSCR1-TFE3). When this disease is no longer amenable to surgical curative intervention, uniformly efficacious therapies are lacking. The aim of this study was to evaluate the expression of potential molecular therapeutic targets in a cohort of ASPS tumour samples. Immunohistochemical analysis for hepatocyte growth factor, c-Met, phosphorylated c-Met, phosphorylated AKT, phosphorylated MEK, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p53 and vimentin was performed on an ASPS tissue microarray, yielding complete data from 26 tumours. Activation of c-Met and its downstream effectors was noted, whereas only limited EGFR expression was seen. VEGF was expressed to varying degrees. Only one sample exhibited strong nuclear p53 expression, while 10 expressed low levels. Vimentin expression was negative in the vast majority of samples (96%). There is a crucial need for better anti-ASPS therapies. Activated c-Met and the phosphorylation of its downstream effectors validate an intact signalling cascade probably induced by the ASPSCR1-TFE3 chimeric transcription factor. The angiogenic phenotype of these tumours is supported by increased angiogenic factor expression. Combination therapies targeting both tumour cells and angiogenesis merit further investigation.Keywords
This publication has 21 references indexed in Scilit:
- Therapeutic Vulnerability of an In Vivo Model of Alveolar Soft Part Sarcoma (ASPS) to Antiangiogenic TherapyJournal of Pediatric Hematology/Oncology, 2009
- Spontaneous regression in alveolar soft part sarcoma: case report and literature reviewWorld Journal of Surgical Oncology, 2009
- Principles of Cancer Therapy: Oncogene and Non-oncogene AddictionCell, 2009
- Gene expression profiling of alveolar soft-part sarcoma (ASPS)BMC Cancer, 2009
- Combination of antiangiogenesis with chemotherapy for more effective cancer treatmentMolecular Cancer Therapeutics, 2008
- New Perspectives for Staging and Prognosis in Soft Tissue SarcomaAnnals of Surgical Oncology, 2008
- The Met tyrosine kinase receptor in development and cancerCancer and Metastasis Reviews, 2008
- High prevalence of p53 exon 4 mutations in soft tissue sarcomaCancer, 2007
- TFE3 Fusions Activate MET Signaling by Transcriptional Up-regulation, Defining Another Class of Tumors as Candidates for Therapeutic MET InhibitionCancer Research, 2007
- Alveolar soft-part sarcoma: a review and updateJournal of Clinical Pathology, 2006