Angiogenesis-promoting gene patterns in alveolar soft part sarcoma

Clin Cancer Res. 2007 Dec 15;13(24):7314-21. doi: 10.1158/1078-0432.CCR-07-0174.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Proteins / genetics
  • Neovascularization, Pathologic / genetics*
  • Oncogene Proteins, Fusion / genetics
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Alveolar Soft Part / genetics*
  • Sarcoma, Alveolar Soft Part / mortality
  • Sarcoma, Alveolar Soft Part / pathology
  • Survival Analysis
  • Tissue Array Analysis


  • ASPSCR1 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • TFE3 protein, human