Angiogenesis-Promoting Gene Patterns in Alveolar Soft Part Sarcoma
Open Access
- 15 December 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 13 (24), 7314-7321
- https://doi.org/10.1158/1078-0432.ccr-07-0174
Abstract
Purpose: We examined a cohort of patients with alveolar soft part sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor. Experimental Design: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation. Results: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique. Conclusion: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.Keywords
This publication has 34 references indexed in Scilit:
- EphA2 overexpression is associated with angiogenesis in ovarian cancerCancer, 2007
- A Drosophila model of the rhabdomyosarcoma initiator PAX7-FKHRProceedings of the National Academy of Sciences of the United States of America, 2006
- Vascular-endothelial-growth-factor (VEGF) expression and possible response to angiogenesis inhibitor bevacizumab in metastatic alveolar soft part sarcomaThe Lancet Oncology, 2006
- Ewing's sarcoma: General insights from a rare modelCancer Cell, 2006
- Differential Induction of Glioblastoma Migration and Growth by Two Forms of PleiotrophinJournal of Biological Chemistry, 2005
- Nonrandom cell-cycle timing of a somatic chromosomal translocation: The t(X;17) of alveolar soft-part sarcoma occurs in G2Genes, Chromosomes and Cancer, 2005
- Discovery of semaphorin receptors, neuropilin and plexin, and their functions in neural developmentJournal of Neurobiology, 2004
- Soft Tissue SarcomasCA: A Cancer Journal for Clinicians, 2004
- Localized Extremity Soft Tissue Sarcoma: Improved Knowledge With Unchanged Survival Over TimeJournal of Clinical Oncology, 2003
- High-Grade Extremity Soft Tissue SarcomasAnnals of Surgery, 2003