title: SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma.
abstract: BACKGROUND
  Synovial sarcomas account for up to 10 percent of soft-tissue sarcomas and include two major histologic subtypes, biphasic and monophasic, defined respectively by the presence and absence of glandular epithelial differentiation in a background of spindle tumor cells. A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas. The translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2. SYT-SSX1 and SYT-SSX2 are thought to tunction as aberrant transcriptional regulators. We attempted to determine the influence of the two alternative forms of the SYT-SSX fusion gene on tumor morphology and clinical outcome in patients with this sarcoma.
  
  
  METHODS
  We analyzed SYT-SSX fusion transcripts in 45 synovial sarcomas (33 monophasic and 12 biphasic) by the reverse-transcriptase polymerase chain reaction and compared the results with relevant clinical and pathological data.
  
  
  RESULTS
  The SYT-SSX1 and SYT-SSX2 fusion transcripts were detected in 29 (64 percent) and 16 (36 percent) of the tumors, respectively. There was a significant relation (P=0.003) between histologic subtype (monophasic vs. biphasic) and SSX1 or SSX2 involvement in the fusion transcript: all 12 biphasic synovial sarcomas had a SYT-SSX1 fusion transcript, and all 16 tumors that were positive for SYT-SSX2 were monophasic. Kaplan-Meier analysis of 39 patients with localized tumors showed that the 15 patients with SYT-SSX2 had significantly better metastasis-free survival than the 24 patients with SYT-SSX1 (P=0.03 by multivariate analysis; relative risk, 3.0). There were no significant correlations between the type of SYT-SSX transcript and age, sex, tumor location and size, whether there were metastases at diagnosis, or whether patients underwent chemotherapy. Histologic subtype alone was not prognostically important.
  
  
  CONCLUSIONS
  The type of SYT-SSX fusion transcript correlates with both the histologic subtype and the clinical behavior of synovial sarcoma. SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas and may also yield important independent prognostic information.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kawai
authors.forename: J
authors.initials: J
authors.lastname: Woodruff
authors.forename: J H
authors.initials: JH
authors.lastname: Healey
authors.forename: M F
authors.initials: MF
authors.lastname: Brennan
authors.forename: C R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: M
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002887:Chromosomes, Human, Pair 18; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C093961:SS18 protein, human; D014157:Transcription Factors; C093962:synovial sarcoma X breakpoint proteins