title: Angiogenesis-promoting gene patterns in alveolar soft part sarcoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, and Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.
authors: Alexander J F
authors: AJ
authors: Lazar
authors: Parimal
authors: P
authors: Das
authors: Daniel
authors: D
authors: Tuvin
authors: Borys
authors: B
authors: Korchin
authors: Quansheng
authors: Q
authors: Zhu
authors: Zeming
authors: Z
authors: Jin
authors: Carla L
authors: CL
authors: Warneke
authors: Peter S
authors: PS
authors: Zhang
authors: Vivian
authors: V
authors: Hernandez
authors: Dolores
authors: D
authors: Lopez-Terrada
authors: Peter W
authors: PW
authors: Pisters
authors: Raphael E
authors: RE
authors: Pollock
authors: Dina
authors: D
authors: Lev
mesh_terms: D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018234:Sarcoma, Alveolar Soft Part / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: C422743:ASPSCR1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C069203:TFE3 protein, human